Tuesday, October 31, 2006

Neandertal & H. sapiens sapiens interbreeding   posted by Razib @ 10/31/2006 09:42:00 PM

Modern Humans, Neanderthals May Have Interbred:
"To me, what happened is that the Neanderthals were [genetically] absorbed into and overwhelmed by modern humans coming into Europe from Africa, and they disappeared through this absorption," Trinkaus said.
Examining the bones, Trinkaus discovered certain features that he believes are Neanderthal elements incorporated into this early Homo sapien.

Features at the back of the woman's skull and in her lower jaw, especially, "are found in high frequency in Neanderthals" but are absent in bones from older groups of Homo sapiens from Africa, he said.

The paper will be on the PNAS site sometime this week, apparently it is behind an 'embargo wall' right now and already in circulation amongst those with special access. This is a morphology story, it seems that individuals with a mosaic of African and Neandertal traits existed in Europe ~30,000 years ago. What does this tell us? If we didn't have the genetic evidence I think one would have to assume that the highest likelihood is that some interbreeding went on. But didn't we learn last week that humans and Neandertals were separate and distinct lineages, with the latter contributing nothing to the genome of the former?

1) Not all regions of the genome are created equal when it comes to a particular phenotype (e.g., if you looked at Y lineages Mexican Americans should be Spaniards, if you looked at mtDNA lineages they should be Amerindians, and yet they are a mix of both when it comes to the vast majority of their genome, the Y & mtDNA just happen to be convenient for genetic analysis).

2) Selection can operate on specific regions of a genome independently from others. This is why you see "selective sweeps" across lengths of sequence while neutrality seems to be operative elsewhere.

3) There nature of genomic sequences shaped by neutral evolution vs. those subject to selective forces can differ a great deal because of the alternative dynamics at work as a function of time. The former can be far more informative about ancestry than the latter because in the case of the latter not all ancestors are created equal.

4) There are always papers in the pipeline which can modulate your priors. One should credit Trinkaus et. al. because of other pieces of data which will come to light in the near future.

Il Principe as a evolutionary force   posted by p-ter @ 10/31/2006 09:20:00 PM

The dynamics of Machiavellian intelligence. Abstract:
The "Machiavellian intelligence" hypothesis (or the "social brain" hypothesis) posits that large brains and distinctive cognitive abilities of humans have evolved via intense social competition in which social competitors developed increasingly sophisticated "Machiavellian" strategies as a means to achieve higher social and reproductive success. Here we build a mathematical model aiming to explore this hypothesis. In the model, genes control brains which invent and learn strategies (memes) which are used by males to gain advantage in competition for mates. We show that the dynamics of intelligence has three distinct phases. During the dormant phase only newly invented memes are present in the population. During the cognitive explosion phase the population’s meme count and the learning ability, cerebral capacity (controlling the number of different memes that the brain can learn and use), and Machiavellian fitness of individuals increase in a runaway fashion. During the saturation phase natural selection resulting from the costs of having large brains checks further increases in cognitive abilities. Overall, our results suggest that the mechanisms underlying the "Machiavellian intelligence" hypothesis can indeed result in the evolution of significant cognitive abilities on the time scale of 10 to 20 thousand generations. We show that cerebral capacity evolves faster and to a larger degree than learning ability. Our model suggests that there may be a tendency toward a reduction in cognitive abilities (driven by the costs of having a large brain) as the reproductive advantage of having a large brain decreases and the exposure to memes increases in modern societies.

But we're all racist   posted by the @ 10/31/2006 09:23:00 AM

Below the fold is the full text of a paper circa 1993 that reports that freshmen college students tend to misattribute political beliefs to professors on the basis of merely factual material presented in class. The results obviously extend to other areas.

When Teaching is Evaluated on Political Grounds

Stanley Coren
University of British Columbia, Vancouver BC, CANADA V6T IZ4

Psychologists and other behavioral scientists who teach courses containing material on individual differences often find themselves presenting research findings that are politically unpopular in today's social climate. For example, segments of most introductory psychology courses deal with intelligence and mental abilities. An honest treatment of this material requires that evidence be presented indicating that both environmental and genetic factors determine intelligence. The evidence for heritable factors in intelligence is supported by data from selective breeding studies using animal subjects, from twin studies, and from family studies. In exploring the implications of this work the lecturer generally presents the evidence that different racial groups score differently on intelligence tests, and then analyzes the factors that contribute to this observed difference. Most researchers (and most textbooks) agree that although environmental factors are important, genetic contributions cannot be ignored, since they play a large role in determining group differences in mental abilities scores./1/ The case is quite similar in the discussion of sex differences in cognitive abilities. There are systematic differences in the pattern of abilities displayed by males and females on standardized tests. Although many of these differences may be environmental in origin or reflect differences in the socialization of males and females, some ability differences appear to be genetically determined. It appears that the disparity between male and female scores on certain abilities measures are the direct consequence of hormonal, neurological, and even brain structure differences between the sexes. The conscientious lecturer interested in presenting the full picture must discuss these physical differences as well as the environmental factors./2/
Potential Evaluation Problems

Unfortunately, in the current political climate on college and university campuses, it appears that the teaching of research on ability differences among racial or sexual groups may have implications for the careers of faculty members. The potential problem arises in institutions that use teaching evaluations as part of the data upon which decisions about tenure, promotion, and merit pay increments are based. This became clear to me during the course of some committee deliberations at my institution, the University of British Columbia (UBC) in Vancouver, Canada.

The UBC psychology department follows teaching evaluation procedures that are common in many universities. One important component in the evaluation process is the mandatory distribution of a questionnaire to every student at the end of each course. Traditionally, students are asked to comment on their perception of a number of aspects of the course and the instructor. Items addressed include the fairness of evaluation procedures, instructor preparation and interest in the material, clarity of delivery, availability during office hours, rapport with the class, and so forth. Comments are numerically coded and summarized. These summaries then become apart of the instructor's permanent file. Student evaluations have often played a pivotal role in tenure and promotion deliberations pertaining to particular faculty members. They are most likely to have a major impact when the candidate is borderline in some other respects, in which case the teaching evaluations may swing the decision in one direction or another.

Probably as a response to social pressures within the university, the UBC teaching committee decided to "modernize" the current course evaluation questionnaire. This revision involved the deletion of several objective items, such as whether the course was organized logically, or whether the final grade was based upon several evaluations or tests rather than a single assessment. More disturbing was the introduction of several items involving issues of sex and race. Thus students were asked to assess whether the instructor used "examples or stories that were demeaning to members of certain racial or cultural groups" or demeaning either to women or to men. Additional items highlighting racial or sexual identity were also included.

To some faculty members the inclusion of such potentially "political" items in the questionnaire seemed inappropriate, for terms like "demeaning" involve certain assumptions and interpretations in which the listeners' biases are as much a factor as the content of the lecture. A student who is told that one racial group does not do as well as another on certain mental abilities tests may well interpret those remarks as "demeaning" to that group. (As president Harry S. Truman once quipped, "I never did give anybody hell. I just told the truth and they thought it was hell.") The committee revising the questionnaire did not perceive any such risk. The chairman of the committee felt that students know the difference between opinion and scientific data and would not negatively evaluate an instructor for presentation of data, no matter the conclusion reached. Thus, despite objections, several items involving race and sex were included in the revised teaching evaluation questionnaire.
Some Concerns

I was quite concerned about the inclusion of such items. My major trepidation was that students would mistake the conclusions reached in presenting material dealing with race and sex as reflecting the attitudes of the instructor rather than objective reporting of scientific data. I was also concerned that such questionnaire items are based upon the presumption that we can ask students of eighteen and nineteen years of age, who are less than a year beyond high school, to answer difficult questions about what constitutes racist or sexist content in a course and whether their lecturer is guilty of purveying such content. Given that society as a whole and many academics and scholars have struggled with these issues for many years and still have not reached a consensus, the validity of this presumption seems dubious. If student judgments lack validity or, worse, if they are biased by the conclusions reached by the research under discussion, this could prove quite disastrous for faculty members who teach about individual and group differences in behavior.

My long-range concern was that the knowledge that such politically charged items are to be used in teaching evaluations would inevitably serve to "muzzle" faculty. The likeliest targets are young faculty who know that their teaching ratings will affect their chances for promotion and tenure. In effect, the inclusion of "sensitive" items could eventually cause faculty simply not to teach certain substantive areas. The fear motivating such behavior is that lectures that reach politically unpopular conclusions will lead some students to apply labels of "sexist" or "racist" to the lecturer.
An Empirical Assessment

As an experimental psychologist it seemed to me that the best way to address this issue would be to collect some data from the very students who would be called upon to evaluate faculty members. In this way I could either clarify the problems inherent in this form of teaching evaluation, or set my own misgivings to rest.

My test sample consisted of 198 students enrolled in an introductory psychology class. There were 109 women and 89 men; the mean age was 18.7 years. Each received a questionnaire. Students were told not to put their names on the survey form, just as they are not required to sign the teaching evaluation questionnaires. The introduction to the survey reads:
University Teaching Questionnaire

Recently, the public and press have brought to light some issues that are important to the normal functioning of the university. Two, which have been mentioned many times, are:


In the minds of many people there are some topics that are appropriate and others that are inappropriate topics for university and college classes.

It has been occasionally suggested that some professors may let their own personal views enter into their teaching, and these views might be inappropriately presented as fact.

Both of these issues are controversial and many individuals hold different viewpoints about them. We are interested in your opinions about these issues.

Below you will find some sample descriptions of lectures that might be given in an introductory psychology course. Consider what you feel your own reactions would be to such lectures and briefly answer the questions below them.

Four simple lecture summaries were presented in paragraph form:


Professor W gives a lecture about learning. In it he notes that simple repetition does not improve learning. He concludes that rereading the textbook several times will not result in good comprehension. He suggests several working techniques and activities that he feels will improve memory.

Professor X gives a lecture about intelligence. In it he describes some evidence for biological factors, such as genes, that affect intelligence. He suggests that although culture and experience are important in determining scores on intelligence tests, genetic factors can be used to explain some portion of the differences in IQ scores that are obtained when different races take intelligence tests.

Professor Y gives a lecture about aging. In it he notes evidence that older individuals have difficulty learning certain material and solving certain problems. He suggests that these differences may reflect a slowing in thinking processes in elderly people.

Professor Z gives a lecture about sex differences. In it he notes evidence that males consistently score better than females on spatial and mathematical tests. He suggests that while societal and environmental contributions should not be ignored, some portion of these sex differences in ability may be due to genetic factors or differences in the brain structure of males and females.

After each lecture summary, several questions were asked. The first was simply, "Is this material appropriate for a psychology course?__Yes__No." The second and third questions were much more open-ended: "What are the professor's reasons or motives for presenting this subject matter?" and "What does this lecture tell you about Professor__ ?"

The results of this survey supported my fears about how students would evaluate faculty members who present unpopular conclusions. The relevant lectures, of course, are 2 and 4. Although each lecture summary contains subject matter that is often taught in introductory psychology courses, lectures 2 and 4 also deal with the more politically sensitive issues of race and sex differences in intelligence and mental abilities.

Before looking at the data, it is important to note that the viewpoints expressed by Professors X and Z in lectures 2 and 4 are quite consistent with data in the behavioral literature. They agree with the conclusions of many researchers and are in accord with several large literature reviews./3/ Many textbooks for introductory psychology courses also present material of a similar nature. Notice as well that these lecture summaries are clearly moderate in tone, and do not contain anything inflammatory or demeaning to any group. Nevertheless, the results suggest that these eighteen- and nineteen- year-old students saw the lectures as much more negative and problematic.
Lecture 2: Evidence for a Genetic Contribution to Intelligence

In lecture 2 Professor X suggests that there is a genetic contribution to intelligence. Although he acknowledges contributions from culture and environment, he concludes that the genetic contribution to intelligence might account for "some portion" of the differences observed in IQ scores between the races. An amazing 38 percent (76/198) of student evaluators felt that this was not an appropriate topic for a psychology course. Furthermore, in the question on the professor's motives for presenting this material and the question about what this lecture indicated about Professor X, 24 percent (48/198) specifically mentioned "racist," "racism," or notions of "racial superiority" as motivating the presentation of this material. Thus the very discussion of genetic and racial differences in intelligence, if the conclusion is that they exist, renders the lecturer a racist in the minds of nearly one-quarter of these students.
Lecture 4: Evidence for Sex Differences in Cognitive Skills

In this lecture Professor Z suggests that there are differences between males and females in spatial and mathematical ability. Although acknowledging the contribution of social and environmental factors, he concludes that "some portion" of these differences may be due to physiological or genetic differences between males and females. Again, the results are quite distressing. Thirty-one percent (62/198) of the class felt that this was a topic that was not appropriate for a psychology course. There was a strong difference between male and female respondents. Forty eight percent (52/109) of females, while only, 11 percent (10/89) of males, felt that the topic was inappropriate. In the discussion of motives, or what this lecture indicated about Professor Z, 26 percent (51/198) mentioned "sexist," "sexism," "anti-women," "putting women down," or the equivalent as the primary motivation for the presentation. Again, there was a strong difference between the sexes, with 94 percent (48/51) of the sexism charges coming from female students. Thus, in the minds of more than a quarter of all the students, and nearly one-half the female students, simple presentation of data and conclusions that are accepted in the experimental psychology literature makes the lecturer a sexist.
Implications for Faculty Assessment

The conclusions that can be reached based on these data should be obvious--and somewhat frightening. It is quite clear that many students, especially the freshmen tested here, cannot separate the scientific evidence presented by an instructor from the instructors own opinions. Also, they make one variety of the "fundamental attribution" error so well-known to social psychologists./4/ In this case, the error involves the belief that the conclusions reached by the lecturer are the conclusions desired by the lecturer. In other words, the observer (here the student) believes that the lecturer must be driven by internal motives consonant with the data he presents.

Based on the data described above, what can we conclude about how students would describe Professor X if asked whether he "used examples that demeaned any racial or cultural group?" How would students evaluate Professor Z if they were asked whether he used any "examples that demeaned women?" Obviously, many students would describe Professor X as a racist and Professor Z as a sexist.

These data, if they are a valid indicator of how students form opinions about instructors based upon the presentation of particular material in class, have dire implications for faculty members whose courses include the topic of individual differences. In light of teacher evaluation forms that require students to draw conclusions about the political and social attitudes of their professors based upon the content of lectures, this situation can have only one outcome. If faculty members are aware of or suspect there are student biases about such material, then a sizable proportion of junior faculty will refuse to teach this material. The same is probably true for senior faculty, who know that poor teaching ratings might adversely affect decisions about merit pay increases.

Where up to a third of your students wilt negatively evaluate you simply for presenting data that reflect the dominant thinking and empirical results reported in the literature, perhaps it is better to select a book that reaches the "politically correct" conclusions. And in lectures, perhaps it is better to "tailor" the data to reach those same conclusions. Or perhaps it is better not to bring up the topic at all, and thus be absolutely sure that no charges of racism or sexism can be leveled at you.

We must ask ourselves and our teaching evaluation committees: What are political questions doing on an instrument that is supposedly designed to evaluate teaching effectiveness? By allowing political interpretations to form a component in our teaching evaluations we effectively subvert the ideal of dispassionate research and teaching. Teacher assessments based on the student's political or social interpretation of the empirical data or on how well the conclusions accord with his preconceptions and social attitudes must lead to suppression of unpopular data.

It seems that the academic establishment has not recognized what Adlai Stevenson knew about the public psyche. He observed, "You will find that the truth is often unpopular and the contest between agreeable fancy and disagreeable fact is unequal. For, in the vernacular, we are suckers for good news."/5/ If teaching evaluations use student opinions about the social or political implications of the material taught, then behavioral scientists will soon find themselves pressured to teach only the "good news" that there are no differences in the abilities of racial or sexual subgroups--even if this involves ignoring or suppressing the bulk of the research data. Thus the evaluation of teaching ability will become nothing more than the evaluation of how well a faculty member's lectures conform to the political norm. It is sad to think that humorist Josh Billings may have been correct when he said, "As scarce as the truth is, the supply has always been in excess of the demand."


1. These issues have been covered extensively elsewhere, as in Robert Plomin, "Environment and Genes: Determinants of Behavior," American Psychologist 44.2 (1989), or the sprightly debate in H.J. Eysenck, The Intelligence Controversy (New York: Wiley, 1981).
2. For an excellent and remarkably balanced review, see Diane F. Halpern, Sex Differences in Cognitive Abilities (Hillsdale, N.J.: Erlbaum Associates, 1986).
3. See Robert Plomin, Nature and Nurture: An Introduction to Behavioral Genetics (Pacific Grove, Calif.: Brooks/Cole, 1990).
4. See L. Ross, "The Intuitive Psychologist and His Shortcomings: Distortions in the Attribution Process," in Advances in Experimental Social Psychology, ed. L. Berkowitz (New York: Academic Press, 1977).
5. Adlai Stevenson, New York Times, 9 June 1958.

Eugenics   posted by Razib @ 10/31/2006 01:07:00 AM

Aziz comments on a RedState post on eugenics, etc. Of interest to GNXP readers? Perhaps.

Monday, October 30, 2006

Asian Nazis   posted by Razib @ 10/30/2006 11:32:00 PM

I just wasted 15 minutes exploring the Uncyclopedia after seeing a referral from the entry on Asian Nazis. A lot of the other stuff is pretty funny too. Check out this snip from the entry on Bangladesh:
Bangladesh holds the world record for the only country which has more people than mosquitos. Mosquitos are the second largest ethnic populace of Bangladesh. The human population is made up of 49% males, 43% females, 6% hermaphrodites and 2% George W. Bush look alikes. The current list of famous Bangladeshis include the pop band The Bangles, the lovable canine actor Benji, [redacted]. Bangladesh hopes to produce another famous person, of an equal calibre, by approximately 2025 AD.

Intermediate progenitor hypothesis   posted by amnestic @ 10/30/2006 09:17:00 PM

A recent Perspective in Nature Reviews Neuroscience presents an alternative to the radial unit hypothesis of cortical expansion. As you may recall, one of the major alterations in gross brain structure as you move toward primates and those particular primates that we hold dear is the large increase in cortical surface area. The increase is not accompanied by a proportional increase in skull size because the increased amount of cortex is folded in on itself to form sulci (crevices) and gyri (hills). Smooth brains are called lyssencephalic. Wrinkly brains are gyrencephalic.

The radial unit hypothesis suggests that the increase in the size of the neocortex is due to an increase in the cells that both give birth to most cortical neurons and provide the scaffold for those newborn neurons to climb to their proper position in the cortex. These radial glia lie next to the ventricles (fluid filled cavities in the middle of your brain, one of the earliest neural structures to form) in an area called the ventricular zone (VZ) and are attached to the ventricles and to the outer surface of the developing cortex. Strangely enough, the area one layer further away from the ventricles is called the subventricular zone (SVZ). During cortical neurogenesis, neurons are created next to the radial glia and migrate up the scaffold. More cortex space can be created by producing more scaffolds. More scaffolds can be made by increasing the amount of time radial glia divide symmetrically to produce only more radial glia rather than neurons or reducing the number of radial glia that die after they are produced. A and B below.

But one potential issue with the radial unit hypothesis is that the ventricles should grow proportionally to the neocortical growth through evolution. This isn't the case. To circumvent this problem, the intermediate progenitor hypothesis suggests that the immediate product of asymmetric radial glia division is an intermediate progenitor rather than a neuron (C above). These intermediate progenitors migrate to the SVZ just above the radial glia and divide symmetrically some more to produce a crop of intermediate progenitors. Wherever you want more cortical neurons you let more intermediate progenitors be produced. Eventually these cells in a way that produces differentiated neurons and they migrate up to their proper position in the cortex. My favorite piece of evidence for this hypothesis is shown below. You can sort of predict where a cortical fold will be by measuring the thickness of the SVZ early in development. Thinner SVZs will be below sulci, and thicker ones will be below gyri.

Not knowing enough to really critique, my only obvious issue is that it doesn't seem like their criticism of the radial unit hypothesis has to be so. It seems possible to me for radial glia to proliferate without increasing the size of the ventricles that much. As far as I know, noone has shown that the ventricle surface is so jampacked with radial glia feet that it can't accomodate a few more. Also worth noting is that both hypotheses suggest that putting off neurogenesis to produce more progenitors might underlie cortical expansion in humans. So at this point, both hypotheses might lead to similar predictions about the particular genes involved.

Buzsaki and Wilson   posted by Coffee Mug @ 10/30/2006 06:51:00 PM

For the die-hards. I taped the Buzsaki and Wilson lectures at the Visualizing and Recording Large-Scale Ensembles short course at SFN. Quality isn't really great and a lot of it doesn't make sense without the slides, but, hey, it's there if you want it:

Buzsaki Intro and Lecture
(mostly about multi-unit recording and unit isolation)
Wilson Lecture (more about the same, but focus on tetrodes and some data)
Buzsaki vs. Wilson (Breakout group with some questions, interesting to hear them converse and joke. Best sound quality I think.)

PhD scientist or fourth-grader?   posted by p-ter @ 10/30/2006 03:45:00 PM

The paper describing the sequence and analysis of the dog genome ends thusly:
For millennia, dogs have accompanied humans on their travels. It is only fitting that the dog should also be a valued companion on our journeys of scientific discovery.
The lamest line in a scientific paper ever?

John Derbyshire is no longer an Anglican   posted by Razib @ 10/30/2006 12:10:00 PM

Derb has a long article up where he answers all the "religion questions" he's had to deal with and chronicles his drift away from Anglican theism. Not quite Rod Dreher level of personal anguish, but Ponurru isn't pleased....

Seeing what you want to see....   posted by Razib @ 10/30/2006 12:03:00 AM

See What You Want to See: Motivational Influences on Visual Perception:
People's motivational states-their wishes and preferences-influence their processing of visual stimuli. In 5 studies, participants shown an ambiguous figure (e.g., one that could be seen either as the letter B or the number 13) tended to report seeing the interpretation that assigned them to outcomes they favored. This finding was affirmed by unobtrusive and implicit measures of perception (e.g., eye tracking, lexical decision tasks) and by experimental procedures demonstrating that participants were aware only of the single (usually favored) interpretation they saw at the time they viewed the stimulus. These studies suggest that the impact of motivation on information processing extends down into preconscious processing of stimuli in the visual environment and thus guides what the visual system presents to conscious awareness.

(via Chris)

Why does this matter? People see what they want to see, and their logic leads them to what they want them to see. Thank god natural science has reality!

Sunday, October 29, 2006

Immigration & the election   posted by Razib @ 10/29/2006 11:49:00 PM

Steve's newest column tackles the next election (and the likely shift toward the Democrats) and its relevance to immigration. Meanwhile, Derb has been talking up Lou Dobbs Democrats. I don't know what to think about this. I haven't talked about immigration much because I've been rather pessimistic of late...but now I'm not sure sure. Perhaps I won't have to make sure that I'm part of the 21st century oligarchy.

Saturday, October 28, 2006

The green bomb   posted by Razib @ 10/28/2006 09:59:00 PM

The New York Times Magazine has a piece on the Iranian bomb and Islamic attitudes toward use of extreme measures in battle. In Infidels: A History of the Conflict Between Christendom and Islam Andrew Wheatcroft suggests that the Islamic attitude toward battle and war lagged the West in regards to a transition to rational and utilitarian paradigm in theory and practice. In other words, medieval values of valor and courage as opposed to victory at all costs persisted longer in the world of Islam than in Christendom, to the disadvantage of Muslim powers after 1500. So it is interesting to see how some Muslim scholars are now rationalizing barbarities, and how most Muslims now accept suicide bombers as martyrs. I bring this up, because as an unbeliever

1) I am always struck by the enthusiasm that followers of "higher religion" have toward assailing or battling those with whom their disagreemants are on the smallest matters of creed or ritual interpretation (to the point where one wonders if the foot soldiers who die for the sake of the creed can even genuinely discern the differences for which they lay their lives down!).

2) ...and yet, there is such slippery ease with which the clerics and intellectuals of said "higher religion" can re-interpret the propositions entailed by their beliefs when the situation warrants. When I was a child in the 1980s many of the more traditionalist Muslims would not accept the taking of pictures because it was idolatry, and yet now the most radical of the ghazis videotape themselves, and it seems clear that this media serves as a focal point of devotion and adoration!

I suppose from the perspective of the unbeliever the question is this: what is the structure and nature of religious beliefs which allows such plasticity which masks itself as rigidity? Consider that Islamic radicals kill ostensibly in the name of a traditional society, but in the process they sanction the usage of non-traditional tactics such as female suicide bombers! To me, the heart of the piece above is that Islamic scholars will expend a great deal of time rationalizing whatever suits their own ultimate needs, so the background implication that there is some true axiomatic logic which demands that a group of believers espouse a particular set of beliefs down a chain of propositions seems ultimately implausible. Though killing will continue in the name of small differences, those differences are themselves subject to the contingencies of the age.

Addendum: Of course, remember that there is a difference between what people believe and what they believe they believe, and what they say motivates and what truly motivates them. Such considerations need to move past the simple analyses of the past such as Freudianism or Marxist materialism, but there various vectors can I think eventually help in constructing a model of the mind as it moves through the social and physical universe.

Oh Nelly, oh....   posted by Razib @ 10/28/2006 05:51:00 PM

I haven't had regular access to cable television since July of 2004. I haven't had regular access to a television since March of 2005. Overall this has been a good thing, I've read more, I've thought more, and oh yes, I've blogged more, than I would have. Nevertheless over the past few months I have started to notice that my "pop culture lexicon" is getting out of date...I am simply cut off from the cultural touchstones of my peers. This isn't all a bad thing, the animal mutterings which pass for speech from most humans are inputs I only marginally process (just enough to respond as if I am actually listening to the vapid stream). Nevertheless, the rise of YOUTUBE and internet video enabled by broadband allows me to "sample" the Zeitgeist of popular culture now and then. So that was how I stumbled upon this Nelly Furtado video, Maneater. I have three immediate responses

1) Jesus fucking Christ!!! (and I don't even believe in that stuff)

2) Watching a video like that makes it clear just how un-sexy most internet porn is. Internet porn, with its anatomical focus is like a super-value meal, a lot of calories for the buck, but fundamentally unsatisfying once the aftertaste kicks in.

3) Southern European women sure do clean up after a good shaving, huh? The contrast of dark hair and light skin is their bane when it comes to the mustache tendency, but it can be quite striking when the lack of hair means they no longer look like a small men....

Addendum: I believe that for best data gathering you should simply start viewing about 60% of the way through.

TangoMan Adds:To add another data point to the analysis see Georgian beauty Katie Melua. Her style tends to emphasis the range of her voice rather than relying on studio gimmickry. This video has a nifty Hannibal Lechter theme and some great video compositing.

I particularly liked the intellectual controversy that surrounded Katie's song Nine Million Bicycles where her lyrics "We are 12 billion light-years from the edge. That's a guess - no-one can ever say it's true" came under public fire from cosmologist Simon Singh for their inaccuracy. In a one time performance Katie reworked her lyrics - "We are 13.7 billion light-years from the edge of the observable universe; that's a good estimate with well-defined error bars/and with the available information, I predict that I will always be with you". Most agreed that they had lost a little zip in translation.

See also this video for a closer examination of what Georgia has to offer the world.

Pelican versus Pigeon: the Video   posted by DavidB @ 10/28/2006 07:21:00 AM

In case the newspaper photos weren't enough, here is a video clip of the pelican-pigeon encounter.

I doubt if the whole incident took anything like the 20 minutes claimed by some witnesses. Eye witnesses are notoriously bad at estimating the duration of events. Based on the video clip, I guess it may have taken up to 5 minutes.

Saxons, Vikings and Celts   posted by Razib @ 10/28/2006 01:16:00 AM

I just received a review copy of Saxons, Vikings and Celts: The Genetic Roots of Britain and Ireland. I won't be talking about it until January as I've agreed to hold it until it starts being marketed after it's published here in the states. But, I do think it is kosher if I report the data which Bryan Sykes repeats from the 19th century work The Races of Britain.

1) Blonde hair is most common in East Anglia and Lincolnshire, with high values in Yorkshire, Cumbria, the north of Scotland and the Hebrides. It is least common in Ireland and Cornwall. Intermediate values can be found in most of England and Wales.

2) When it comes to eye color the cline is different. Brown eyes are common in the south and the east, where they exceed 40% in East Anglia and Cornwall. In Ireland, Yorkshire and Cumbria the frequency of blue or grey eyes rises to 75%.

If you want a genetic moral from all this it is that eye color and hair color are not closely linked. There does seem to be some correlation between areas with a high frequency of red hair and light eyes (e.g., Scotland), but that is likely because the former trait is derived from a serial loss off function for melanin production on several loci, and light eyes are a natural byproduct of this genetic architecture. There are implied modal combinations, such as many dark eyed blondes in East Anglia, and the dominance of dark haired but blue eyed folk in Ireland, and the dark eyed and dark haired Cornish. Since I have British readers I will leave it to them to judge the accuracy of these ascertainments, though keep in mind that the data was collected in the late 1800s, so population movement might have homogenized the distribution of traits a bit.

Friday, October 27, 2006

Black & white twins   posted by Razib @ 10/27/2006 06:38:00 PM

We've received a lot of search engine traffic over the past few days because of the phenomenon of "black" and "white" fraternal twins (two cases within the last week). Aside from the original post on this blog, I've commented on it a few times at my other blog, here, here and here. Also, some of you might find this 20/20 segment on the original British twins interesting, click on the video. I can't but help wonder if Brazilian readers don't find the commotion a bit amusing...

Tail effects   posted by the @ 10/27/2006 05:49:00 PM

There's another article in Science about women and science.

It appears to consist predominately of (1) rebuttals to straw-men arguments and (2) Lewontin-like claims that we're all the same despite our differences. A great deal of the text deals with describing (without much detail) male-female differences on a variety of criteria.

The magnitude of each gender difference was measured using the d statistic (6), d = (MM - MF)/sw,where MM is the mean score for males, MF is the mean score for females, and sw is the pooled within-sex standard deviation. The d statistic measures the distance between male and female means, in standard deviation units.

They list a variety of metrics on which the sex-difference (measured in d) is small. They fail to mention the male advantage in spatial ability, but do mention the male advantage(?) in aggression. While focusing on differences in measures of ability among children, they relegate discussion of tail effects to the supplemental online text. There they mention tail effects as an effect of differences in variance, but ignore the fact that mean differences also cause tail effects.

Rather than dig any deeper into this paper, I will present what they chose to ignore: the theoretical effects of small differences in mean and variance between males and females will produce large differences at the tails of a normally distributed trait.

This table presents the percentage of females above a +3 SD threshold as various differences in mean (pink) and SD (orange) in standardized units units. Thus, if the mean and SD are equal (0,0) then women make up 50% of the population above 3 SD on this imaginary trait. But if d=0.3 and males have a variance that is 0.06 SD units greater than women, then the female percentage above 3 SD will be 17.1%. A d of 0.3 is labeled "small", and an SD difference of 0.06 (women SD = 0.97, men SD = 1.03) would be hard to establish in small samples. Nonetheless, it would produce exactly the kind of large differences in male:female ratios among the most talented individuals that we observe in math-heavy disciplines.

3.00 0.00 0.02 0.04 0.06 0.08 0.10
0.00 50.0% 45.1% 40.3% 35.6% 31.2% 27.1%
0.05 45.9% 41.1% 36.4% 31.9% 27.8% 24.0%
0.10 41.9% 37.2% 32.7% 28.5% 24.6% 21.1%
0.15 37.9% 33.4% 29.2% 25.2% 21.7% 18.5%
0.20 34.1% 29.9% 25.9% 22.3% 19.0% 16.1%
0.25 30.6% 26.5% 22.9% 19.5% 16.6% 14.0%
0.30 27.2% 23.5% 20.1% 17.1% 14.4% 12.1%
0.35 24.1% 20.6% 17.6% 14.9% 12.5% 10.4%
0.40 21.2% 18.1% 15.3% 12.9% 10.8% 9.0%
0.45 18.6% 15.8% 13.3% 11.1% 9.3% 7.7%
0.50 16.2% 13.7% 11.5% 9.6% 8.0% 6.6%

Neandertal genome sequencing   posted by Razib @ 10/27/2006 12:38:00 PM

Afarensis points me to this new story in National Geographic about the Neandertal sequencing effort:
A new study by geneticist James Noonan at Lawrence Berkeley National Laboratory, however, reveals that modern humans and Neandertals' most recent common ancestor probably perished about 400,000 years ago.
Noonan's work represents a significant advance over earlier studies of Neandertal genetics, such as those conducted by William Goodwin of the University of Glasgow in Scotland....

That early work involved analysis of mitochondrial DNA, which tends to stay preserved longer than DNA found inside the nuclei of cells. But Noonan analyzed nuclear DNA, which holds a much greater wealth of information.
Based on his results to date, Paabo expects to see some surprises as his project proceeds.

"Neandertal DNA is degraded in specific ways that we had not anticipated, and in some ways Neandertals actually look closer to humans than we had expected," he said.

What could Paabo mean??? Stay tuned over the next few weeks....

Thursday, October 26, 2006

Flavor   posted by Razib @ 10/26/2006 09:05:00 PM

On In Our Time with Melvin Bragg the host often asks his guests to give him a "flavor" of the debate amongst scholars. I always feel that this is acceptable when they are talking about history (e.g., The Diet of Worms), but somewhat bristle at the presumption when it comes to science (e.g., Galaxies). I suppose that I feel that much of scientific work on an advanced level, when science become more than just natural philosophy, is beyond simple intelligibility via sampling a "flavor." In other words, the necessary contigency of scientific debate makes is rather difficult to extract out a portion to impart the quality of the argument. In contrast history is a bundle of facts with little theoretical unity, so one can more easily capture via sampling the rough distribution of the debate. Agree or disagree?

Viruses and memory   posted by p-ter @ 10/26/2006 06:04:00 PM

See Aetiology for the details.

Mice, men, and man's best friend   posted by p-ter @ 10/26/2006 04:41:00 PM

In 2004, a group based out of Bruce Lahn's lab published a paper arguing that nervous system genes had experienced accelerated evolution in primates, particularly on the human lineage. Their approach was based on the following observations: humans and macaques diverged about 20 million years ago, as did mice and rats. But the changes in brain morphology are strikingly different in the two taxa (see their figure on the left). So they compared the evolution of a set of genes expressed in the nervous system in rodents with the evolution of the same genes in primates. Their set of 200-some genes was chosen based on a number of criteria, including expression studies, literature searches, and the inclusion of genes mutated in known neurological diseases.

As a sort of control, they did the same analyses on a number of "housekeeping" genes-- genes that perform important cellular processes, and thus are likely to be evolving under strong evolutionary constraint. Their results were consistent with their predictions-- nervous system genes, in general, evolved faster in primates than in rodents, while housekeeping genes evolved at about the same rate in both taxa. They then further broke down their group of nervous system genes into those involved in neurodevelopment, those involved in physiology, and those that they couldn't classify. Strikingly, it seemed that the difference between primates and rodents was most pronounced in neurodevelopmental genes. The group then nominated genes with particularly accelerated evolution in primates as candidates worthy of further study. 17 of these 24 are involved in regulating brain size or behavior, a particularly interesting finding. Of course, they then followed up on some of them.

It seems an odd time to attack this study as unjustified, but that's exactly what a new paper attempts to do. They claim the Lahn paper has four major shortcomings; I present them here in bold, with my comments afterwards:

1. "First, they compared only 24 nervous system genes between human and chimpanzee--the most relevant species pair for studying evolution of the human brain"

It's true the original paper is based on a human-macaque comparison (they then compare their 24 outliers with chimps), but they justify this as follows:
Recent discussions surrounding the genetic origin of humans have placed a great emphasis on human-chimpanzee comparative genomics. Undoubtedly, this approach has revealed-and will continue to reveal-genetic differences that might underlie the biological distinctions between these two sister species. Because of the exceedingly high degree of sequence identity between human and chimpanzee genomes, however, comparative studies often lack statistical power, and in many cases would overlook genetic differences that bear biological relevance. The issue of weak statistical power in human-chimpanzee sequence comparisons has been noted before (Shi et al., 2003) and is supported by our simulation studies showing that the average stochastic variance in Ks as a fraction of the true underlying mutation rate is about twice in human-chimpanzee comparison as it is in human-macaque comparison (our unpublished data). Relative to human-chimpanzee comparisons, our approach offers two important advantages. First, the use of a more distant primate species for comparison with humans provides the much needed statistical power for determining the evolutionary significance of sequence changes.
Further, while human-chimp comparisons are certainly valuable, it's worth noting that we are extremely similar to chimps, and the evolutionary trends leading to modern humans are likely to have been present long before the human-chimpanzee divergence.

2. "Second, their list of nervous system genes was manually compiled and might thus be incomplete or biased"

The new paper claims to make an unbiased complilation of brain expressed genes and show that, in this compilation, there is no acceleration for nervous system genes. I don't feel like I'm really in a position to judge this claim, except to note that, well, the "small, biased gene set" used by Lahn's group contained a lot of genes that have later been confirmed to be under selection. There's certainly a difference in goals between the two groups: Lahn's group sought to identify candidates to follow up, thus they used specific hypotheses about which genes to include, while this group looks to comment on broad patterns in human evolution. That is, they want to say that many amino acid changes in many genes are not involved in human brain evolution. Lahn identified 24 of them; maybe that's not enough to claim "a lot", but it's certainly an interesting set of genes to examine.

3. "Third, they used house-keeping genes as controls in some of the analyses, which seems inappropriate because tissue-specific genes and house-keeping genes are expected to have different evolutionary patterns"

Yes, tissue-specific genes and housekeeping genes are supposed to have different evolutionary patterns, in that houskeeping genes are supposed to be under more constraint. That is, indeed, the point of using them as a control.

4. "Fourth, a recent comparison between the dog and mouse genomes found that 18 nervous system genes that evolved faster in primates than in rodents also evolved faster in carnivores than in rodents, suggesting that the findings of Dorus et al. [the Lahn paper] might partially be due to rodent deceleration rather than primate acceleration"

I'm glad this point came last, because it's particularly interesting. So the domestic dog has experienced an acceration of nervous system genes relative to rodents. The authors seems to think this implies a deceleration of evolution in rodents. The other possibility, of course, is that evolution was accelerated on the dog lineage as well as on the primate lineage. I don't know too much about the ancestral species leading to dogs, but it's worth noting that the domestic dog has been under intense artificial selection for behavioral traits in the last 100,000 years. So perhaps the molecular substrates underlying dog domestication and human domestication (because essentially, our recent evolution has been a "domestication") are similar. I find this hypothesis much more enticing.

Face blindness   posted by Razib @ 10/26/2006 09:50:00 AM

Long article on face blindness in Wired.

LTP protein story breaks down   posted by amnestic @ 10/26/2006 07:50:00 AM

The new Neuron has a bunch of good stuff in it. I don't understand how they expect me to do lab work if they keep giving me all this good junk to read. I think the PI for this report was Tobias Bonhoeffer. It's a short paper with just a few experiments but it has wide implications. The standard story is that activity related to memory storage should cause protein synthesis and those proteins are used to build the changes into synapses to make a lasting change in cellular response to input. Some papers recently have shown that protein degradation may be as important for long-term potentiation (the cellular model for memory) as protein synthesis. Besides the Bingol and Schuman paper linked above there is the example in drosophila of an activity-dependent degradation of the protein, armitage, which released CaMKII RNA from translational repression (Ashraf et al, 2006).

In the Bonhoeffer paper, they did the normal thing experiment where you block the longest lasting form of LTP (late-LTP) with a protein synthesis inhibitor. But then they also tried the same experiment with a protein degradation inhibitor in the solution as well. BooyaShocka! The late-LTP was back to normal levels. Activity must be degrading proteins that could've been used for synaptic plasticity. This is really odd. I don't really know how to interpret it yet. A cluster of synapses could be sharing proteins and so very local degradation could increase specificity of a modification, just like you can add inhibition to a neural network to increase your signal to noise ratio, but when protein synthesis and degradation are both inhibited perhaps the synapses that need to be modified just borrow from their neighbors instead of making new proteins. The proteins that are degraded must be the same ones that are being synthesized as if the overall metabolic rate is increased rather than any specific synthesis. One wonders if there is any sort of local cellular metabolic stress state due to use of amino acids and ATP in these processes.

If this was the case then you could do an interesting "synaptic competition" experiment where you establish LTP in one input and then establish it in a second input under the influence of synthesis and degradation blockers, perhaps the second input would pull some of the material away from the first. This will take some time to digest. The need for protein synthesis was just on the verge of dogma in the field of synaptic plasticity. At the very least, we can expect a much more detailed study of the proteasome (the protein degradation machinery) at synapses in coming months/years.

Wednesday, October 25, 2006

Charles Darwin Online   posted by Razib @ 10/25/2006 11:45:00 PM

Well, you know that The Complete Work of Charles Darwin Online is now live, right? But remember to give some love to the R.A. Fisher Digital Archive, where you can read his genetical and non-genetical papers. Also, keep an eye over at Abebooks for cheap copies of The Genetical Theory of Natural Selection. They're all north of $65 US dollars right now (that's like $2,000 Canadian right?), but I got my copy for $33, so just keep checking.

Four Stone Hearth   posted by Razib @ 10/25/2006 11:39:00 PM

Four Stone Hearth, an (the?) anthropology blog carnival is up and running. Our friend Yann Klimentidis has a contribution!

Synaptic whack-a-mole   posted by amnestic @ 10/25/2006 09:27:00 PM

A recent paper in Neuron provides a note of caution when interpreting gene knockout studies, a hint of the impact RNAi technology has on a field of study, and some new tidbits about AMPA receptor trafficking. Previous studies has shown that overexpressing a protein called PSD-95 (post-synaptic density - 95 kDa) led to an increase in synaptic AMPA receptors. AMPA receptors are responsible for a major portion of the excitatory neurotransmission in the brain. They normally respond to pre-synaptic glutamate release by opening a pore through their center and allowing sodium into the cell, thereby depolarizing the post-synaptic neuron and increasing the probability that it will fire an action potential. Increases in synaptic AMPA receptor content are likely to explain the increased synaptic response observed in long-term potentiation (LTP). Since PSD-95 seems capable of modulating this factor it has attracted much interest.

PSD-95 is part of a larger family of proteins called PSD-MAGUKs that also includes PSD-93, SAP102, and SAP97. MAGUKs don't seem to have a catalytic activity. Rather, they are likely to serve as scaffolding proteins, connecting one protein to another through multiple binding sites up and down the MAGUK sequence. All PSD-MAGUKs share similar binding domains but vary in the details. Part of the impetus for the present paper is that a transgenic mouse with targeted disruption of the portion of PSD-95 that ought to interact with AMPA receptors shows no signs of difficulty in synaptic transmission. Now, thanks to these authors, we have a mouse that lacks PSD-95 altogether and still no deficit in AMPA receptor delivery.

Long story short, PSD-93 is picking up the slack when PSD-95 is knocked out. It's compensation. Redundancy and degeneracy are the rule rather than the exception in biological systems. This set of experiments makes it so clear that a knockout mouse is never what you expected you were making. There is no deficit in a PSD-93 knockout either. Only in the double knockout (mice lacking PSD-95 and PSD-93) do you get a significant decrease in AMPA receptor transmission, and in that case SAP-102 still pops up and does its damnedest to keep the synapses running on time.

The way all of this was discovered was through the use of more acute gene knockdown using short hairpin RNAs expressed via a viral vector. You can create a virus that will code for something that looks tasty to the RNA interference machinery like an shRNA and infect a slice of brain tissue with it. RNAi machinery will grab the shRNA, chop out a 22 base sequence from it, and go around translationally repressing or destroying any RNA that matches that sequence. So you can get gene specific knockdown quick enough in the adult preparation and not allow the neuron time to compensate by upregulating a redundant gene. As opposed to knocking out PSD-95 from day 1, shRNA targeted against PSD-95 drastically decreased excitatory synaptic transmission. The same goes for PSD-93. Knocking down SAP-102 with shRNAs in the PSD-93/PSD-95 double knockout almost completely eliminated any sign of synaptic AMPA receptors. One of the most interesting control experiments in the study was to use shRNA against a gene that was already knocked out (i.e. PSD-95-shRNA in the PSD-95-KO). This invariably produced no effect, showing that the shRNA manipulation was specific.

When SAP-102 isn't rescuing PSD-93/95 double knockout mice from oblivion, it has a day job. It is normally expressed earlier in development (peaking at 10 days post-natal). There is a developmental switch in which MAGUKS are the prominent AMPA receptor traffickers, so after SAP-102 for a couple weeks, PSD-93/95 come on and take over synapse scaffolding duty. In normal mice, shRNA against SAP-102 only has an effect in the early developmental timepoint.

Also, in the normal mouse, PSD-95 shRNA doesn't completely block AMPA receptor currents and neither does PSD-93 knockdown. This suggests that normal mice have a heterogeneous population of synapses, some of which utilize 93 and others that use 95. It would be interesting to know if there is any functional or localization difference between a 93 and a 95 synapse. While one of the major messages of this paper is that these proteins can compensate for each other seamlessly at least in the assays performed thus far, it seems unlikely that they will perform the exact same function in their natural setting.

Behavioral Innovation in Pelecanidae   posted by DavidB @ 10/25/2006 01:29:00 AM

Pelicans eat fish, right? Don't count on it, especially if you are a pigeon...

Tuesday, October 24, 2006

The adaptive landscape & Iraq   posted by Razib @ 10/24/2006 09:37:00 PM

Salamander Candy has a post attempting to use the heuristic of the adaptive landscape in relation to Iraq and its political organization. These analogies of course have resonance in direct proportion to familiarity. Myself, I tend to imagine sociological systems like the boat vs. chair conformation.

Blood of the Isles   posted by Razib @ 10/24/2006 09:31:00 PM

I was contacted about the new book by Bryan Sykes Blood of the Isles because of my post blood of the British, and I noticed that the book's website has data sets freely available of the mtDNA and Y results from the genetic survey.

Monday, October 23, 2006

The New Atheism   posted by JP @ 10/23/2006 09:29:00 PM

Via Hit and Run, a Wired article: Battle of the New Atheism. The author talks with Dawkins and Dennett.

More neuronal microRNAs on the way   posted by amnestic @ 10/23/2006 07:23:00 PM

One poster at the SFN conference last week described a microRNA (miR132) discovered using a novel screening technique for learning related genes that controls dendrite growth and production of new synapses. The method is called Serial Analysis of Chromatin Occupancy (SACO). The team that first produced SACO in 2004 focused on a transcription factor called CREB (CyclicAMP Response Element Binding Protein, this is NOT CPEB). Part of CREB's popularity stems from the emphasis it has received as a sort of final common path for long-term memory processes in the scheme presented by Eric Kandel in his Nobel work. In that view, CREB is activated by signaling pathways initiated during learning, such as the cyclic-AMP dependent protein kinase (PKA). Activated CREB then goes to the nucleus and sits next to parts of the genome that it wants to regulate up or down. Soren Impey and Daniel Storm showed a few years ago that mice carrying a reporter gene (lacZ) with 6 places for CREB to sit (CREs) in front of it showed more reporter expression in the hippocampus following learning than following simple stimulus exposure. There are many questions as to why you would want to bother to regulate genes at the transcriptional level in response to learning. It seems slow and clunky compared to translating a pre-existing RNA near the affected synapses, but the level of many transcripts does change in the minutes to hours following learning or induction of synaptic plasticity. One assumes it is not for nothing.

When a transcription factor like CREB settles down on the DNA you can play a dirty trick and glue it to its seat using formaldehyde. In the initial SACO study, they activated CREB using a drug that activates PKA and then glued it to all the different parts of the DNA that it lighted upon. They then pulled CREB and whatever DNA would come with it out of solution and sequenced 21 nucleotide strings of it. 21 nucleotides turns out to be just enough to uniquely identify a region in a large genome. These segments represent candidate CREB binding sites, especially if the same segment comes up multiple time. So they sorted through all these potential CREB binding sites and found that most of them were either in genes or near them, so that was nice. Some of the SACO-identified sites were near microRNAs. One of those microRNAs is miR132 and (I guess because it has such a pretty name) Impey and co decided to follow it up.

In the SFN poster, they showed an increase in miR132 with neuronal activity. Activity in cell cultures (where most of this work was done) can lead to dendritic growth and production of new synapses, but not if miR132 isn't around. The straightforward story then is that activity activates CREB which goes to the nucleus and causes transcription of miR132 which then must come out and inhibit the translation of some protein? They used several predictoin algorithms to try and pick out what neuronal gene miR132 might antagonize and came up with a protein called p250GAP. We'd have to get involved in a whole other signaling pathway to explain what p250GAP does, but let's just say that it is in prime position to regulate the cytoskeleton and therefore dendritic and synaptic morphology. Note that miR132 works in the opposite direction from miR134 in terms of synapse growth (although they could be active at different times and in different areas). Reports in Drosophila that RNA interference associated machinery is degraded in response to activity raised the possibility that RNAs that promote synaptic growth and strength could be regulated as a group by RNAi and released from inhibition in concert. But alas, with microRNAs having opposite functional effects the appealing idea of coordinated regulation seems less plausible now.

Dawkins v. Colbert   posted by amnestic @ 10/23/2006 06:59:00 PM

In case you were asleep. Dawkins may be right, but Colbert won anyway.

Update from Razib: Dawkins on the radio.

Regulatory or protein-coding change?   posted by JP @ 10/23/2006 05:29:00 PM

I just came across another argument for why the regulatory changes vs. protein coding changes argument is inane-- sometimes protein-coding changes are regulatory changes. Ok, maybe RPM made that point in the comments on that post I linked, but here's a great example, from a recent paper:

The authors looked for local regulatory variation in a number of genes, and found one instance where the putative regulatory variant mapped to a protein-coding SNP inside the gene. On a little further study, they found the story goes like this-- the gene itself (AMN1) is a regulator of two other genes (DSE1 and DSE2) in a network, and those genes, in turn, regulate AMN1. The coding change in the gene keeps it from playing its proper role in the network, so DSE1 and DSE2 are upregulated and, in turn, up-regulate AMN1. I'm sure there's an easier way to explain this, but the take-home message is that a protein-coding change in AMN1 leads, indirectly, to it's own regulation.

So the genetics underlying gene expression can be rather complex. And just think, it's networks of interacting genes that lead to phenotypes--the complexity is rather daunting, and I feel like first understanding gene expression is certainly a great first step towards getting at phenotypic complexity itself (there's another great first step, but no one seems to have taken it...yet). For those who simply must know more, here's a great review of the current knowledge on the genetics of gene expression.

Sunday, October 22, 2006

Leprosy and Scandinavian babes   posted by agnostic @ 10/22/2006 10:10:00 PM

Speaking of the ubiquity of recent selection, I'm in the middle of looking at the recent selection of various traits that have to do with sexiness in different parts of the world. The primary selection pressure concerning physical attactiveness is, of course, pathogen prevalence -- what stronger force could there be for making us care about how hot a person is? Since the sexiest birds evolved in the tropics -- areas of high pathogen prevalence -- there is no reason to think that humans would turn out any differently, to a first approximation. Hamilton & Zuk (1982) proposed that ornateness was a signal of health in more germ-ridden species, and that mates would choose the more ornate individuals to give their offspring a leg up in chasing the moving target of evading pathogens. (They looked at variation in pathogen prevalence in North American birds, not those from the tropics, but it's clear which species are more decorated.)

Continuing in that vein, Gangestad & Buss (1993) showed that the degree to which individuals (both male and female) emphasized "good looks" in a potential mate correlated highly with local pathogen prevalence. The correlation is not caused by latitude or climate per se but truly by the pathogen prevalence -- the raw correlation is +0.38 (p less than .05), but when controlling for the possible confounds of latitude, geographical region (e.g., Africa, Europe, etc.), and average income, the correlation becomes +0.72 (p less than .001). If the effect were merely due to differences in latitude, continent, etc., then the correlation should decrease in magnitude, whereas it nearly doubles. The obvious corrollary, which Gangestad & Buss don't mention, is that populations adapted to historically more pathogen-stricken areas will on average be more physically attractive, since both sexes emphasize (and thus, probably choose based on) good looks in a partner. To my knowledge, no one has showed that yet, but I plan to shortly by analyzing data on how different countries have faired in the Miss Universe contest.

However, Scandinavia would appear to be a glaring exception -- though pathogen pressures have been less severe than in the Mediterranean, they fair well in beauty contests and are thought of by non-Scandinavian whites (and maybe other groups) as more beautiful than other Northern European groups. (See the Appendix for the Miss Universe-derived scores of Northern European countries.) And yet, there is an exception to this exception -- Scandinavia was the one holdout in Europe for leprosy, which continued pretty much up to the start of the 20th C. From William McNeill's Plagues and Peoples (p.185):

Hansen's disease appears to have established itself in Europe and the Mediterranean coastlands in the sixth century A.D. Thereafter, together with other infections classified as leprous, it remained of major importance until the fourteenth century. Leprosaria were established outside thousands of medieval towns. By the thirteenth century one estimate puts their number in all of Christendom at 19,000.

And though leprosy faded in most of Europe in the 14th C (p.186),

Hansen's disease did continue to exist, on a significant scale, in Scandinavia and more sparsely in other parts of Europe as well.

The Encyclopaedia Britannica article on leprosy agrees that leprosy continued in Scandinavia after it had begun to subside elsewhere in Europe during the 14th C. McNeill guesses that it could have continued due to the practice of huddling close together every night to keep each other warm, since leprosy requires prolonged contact with an infected person to be transmitted to the next host. It is no accident, then, that the physician who discovered the microbial cause of leprosy, Armauer Hansen, was a Norwegian who worked in the historically largest city of Norway -- Bergen -- since it is difficult to conduct painstaking research where there are few subjects to investigate. So, though low overall in pathogen prevalence, Scandinavia had a much higher prevalence of leprosy from Medieval times almost right up to the present.

Of course, leprosy is a disfiguring skin disease, one that would have made a sufferer a virtual Darwinian dead-end, as no one would want to mate with them. Scandinavian males today, as shown by Buss' (1989) [pdf] cross-cultural survey, do not care much about whether or not a potential partner is good-looking (and of course, neither do the females), in line with the historically low pathogen prevalence of their environment. However, no matter how willing Scandinavians may be to overlook sub-perfect breast development, graying hair, and so on, damn few would be so openminded as to willingly mate with a leper. Our modern sensibilities are offended by the sight of mere genital warts -- imagine viewing a nude person with festering sores encrusting a fair fraction of their body. Talk about a selection pressure! Especially when this pressure lasted for at least 700 to 1000 years, or from 28 to 50 generations depending on exactly how long and whether a generation equals 20 or 25 years; and particularly in a population that experienced little inward gene-flow.

The only study to attempt to quantify the narrow-sense heritability (or h^2) of good looks, using a twin design, is McGovern et al (1996), which showed a DZ concordance rate of 0.33 and a MZ concordance rate of 0.65. The broad-sense heritability = 2(MZ - DZ) or 0.64, and since the MZ rate is almost exactly twice the DZ rate, we can assume that most of this genetic component is additive, so let h^2 = 0.64. The Breeder's Equation

says that the response to selection R, equals the selection differential S (or how high the parents' mean is above the population mean) multiplied by h^2. If leprosy was a strong enough pressure so that the parents' mean would have been at just the 52.2 percentile, then S = 0.0558 SD; this multiplied by h^2 of 0.64 = 0.035712 SD increase in attractiveness per generation. Multiply that by 28 generations of selection, and the overall increase is 1 SD, comparable to a gain of 15 IQ points or 3 to 4 inches of height. If the selection lasted for the rough upper-bound of 50 generations, then the parents in each generation would only had to have placed in the 51.2 percentile -- barely above-average in either case.

Some caveats: this assumes minimal inward gene-flow from populations not also subject to leprosy pressures, which would have blunted the response to selection. However, inward gene-flow from other Northern European countries wouldn't have mattered much up to about 1400, since other regions were also plagued by leprosy. From 1400 to 1900, I can't find estimates of gene-flow into Scandinavia (though I'm sure they're in the literature), but it must have been very low, as this region is one of the most homogenous. The pressure probably relaxed around 1900, after the infectious nature had been discovered and medical intervention began wiping out the disease. Still, that's only 4 or 5 generations ago, hardly enough time to undo 28 to 50 generations of directional selection, and surely good looks were not selected against during the 20th C. Last, it would be desirable to uncover independent confirmation that Scandinavians were more affected by leprosy pressures than other Northern Europeans. There are genes in the HLA that are implicated in susceptibility to leprosy, but I couldn't find allele frequency distribution data on ALFRED. By hypothesis, Scandinavians would show greater frequency of such alleles compared to other Northern Europeans (at least the populations included in the chart below).

Finally, we don't have a convenient metric of attractiveness, let alone data on the difference in means across various populations, but this simple calculation shows that it's entirely feasible for Scandinavians to have risen 1 SD above their previous Northern European mean. Of course, populations outside Northern Europe may have already undergone substantial selection for attractiveness (also due to pathogen pressure) before leprosy hit the scene in Northern Europe, and continued to experience such selection up to 1900 and maybe beyond. So, the claim is not that selection has made Scandinavians the most attractive population on Earth, but at the very least the most attractive of Northern Europe.

Appendix: While admitting that attractiveness will always remain somewhat subjective and more prone to errors of measurement than gauging height, there are universals in what features are considered attractive. Citations would be irrelevant (though you can look up Buss, Thornhill, Singh, and others if you're skeptical). Hair-splitting aside, it's not as if maculated skin, beady eyes, or a waist that's pronouncedly wider than the hips are considered attractive by the world's cultures. The Miss Universe pageant is one of the few arenas where individuals representing the world's populations are subject to the same criteria, and where the scores reflect the preferences of the same target audience. True, there could be a non-trivial chance component since only one individual serves as a delegate for their entire population, not to mention the whims of the judges. Before the Civil Rights and national liberation movements of the 1960s, there may also have been a bias toward those of European descent (Miss Universe began in 1955). Nevertheless, the latter does not factor in here, as all countries are Northern European. And to remove as much of the chance component as possible, only countries who had entered 20 Miss Universe pageants were considered -- 1 win out of 4 contests might represent a fluke, but Sweden's 3 wins and 28 semi-finalist placings out of 54 contests cannot be a fluke.

The hotness score H was determined as follows:

Where W = number of wins, S = number of semi-finalist placings (S is multiplied by 0.1 to make sure semi-finalist status did not trump winner status), C = number of contests entered, and P = size of country's population in millions as of the past three years. W, S, and C were culled from a website of Miss Universe statistics, and the population estimates were gotten from the country's Wikipedia entry. The numbers inside the parentheses represent the country's raw placing score per contest entered per unit of population, and since it varies by orders of magnitude, the (natural) log was taken, and this multiplied by -1 to remove the negative sign (for ease of inspection). This simplifies to the second line of the graphic. Lower H scores represent greater hotness -- akin to 1st place being the greatest and 10th place the worst in a 10-contestant race. Below is a chart of Northern European countries ranked in ascending order of H scores (right column) -- that is, in descending order of hotness. Again, don't take the ranking too seriously, but it's clear nonetheless that the Scandinavian countries really are, in some sense, hotter than the other Northern European countries.

Country W _ S _ .1S _ W+.1S _ C _ P _ H

Iceland 0 _ 4 _ .4 _ .4 _ 40 _ 0.3 _ 3.401
Finland 2 _ 18 _ 1.8 _ 3.8 _ 51 _ 5.3 _ 4.265
Sweden 3 _ 28 _ 2.8 _ 5.8 _ 54 _ 9.1 _ 4.439
Norway 1 _ 17 _ 1.7 _ 2.7 _ 49 _ 4.7 _ 4.446
Wales 0 _ 5 _ .5 _ .5 _ 30 _ 3 _ 5.193
Scotland 0 _ 5 _ .5 _ .5 _ 29 _ 5.1 _ 5.690
Denmark 0 _ 7 _ .7 _ .7 _ 41 _ 5.4 _ 5.757
Switzerland 0 _ 10 _ 1.0 _ 1.0 _ 46 _ 7.3 _ 5.817
Netherlands 1 _ 11 _ 1.1 _ 2.1 _ 48 _ 16.3 _ 5.920
Ireland 0 _ 7 _ .7 _ .7 _ 46 _ 6 _ 5.977
Austria 0 _ 7 _ .7 _ .7 _ 38 _ 8.3 _ 6.111
Belgium 0 _ 7 _ .7 _ .7 _ 52 _ 10.4 _ 6.650
England 0 _ 19 _ 1.9 _ 1.9 _ 36 _ 50.4 _ 6.862
Germany 1 _ 21 _ 2.1 _ 3.1 _ 55 _ 82.4 _ 7.288
France 1 _ 12 _ 1.2 _ 2.2 _ 55 _ 63.6 _ 7.371
Poland 0 _ 4 _ .4 _ .4 _ 23 _ 38.1 _ 7.692
Luxembourg 0 _ 0 _ 0 _ 0 _ 27 _ 0.5 _ UND

I wanna sex you up   posted by Razib @ 10/22/2006 07:01:00 PM

Dude sings like a girl....

The Devil under form of Baboon is our grandfather!   posted by JP @ 10/22/2006 11:25:00 AM

Adam Gopnik has an excellent essay in the most recent New Yorker arguing that Charles Darwin, while cultivating an image of an unassuming naturalist forced, by the facts, to reluctantly revolutionize modern thought, was really, well, a Darwinian fundamentalist. The article isn't available online, but it's worth a little effort to find. A couple excerpts below the fold.
Darwin's strategy was one of the greatest successes in the history of rhetoric, so much that we are scarcely aware that it was a strategy. His pose of open-mindedness and ostentatiously asserted country virtue made him, in his way, as unassailable as George Washington. The notion persists to this day that Darwin was a circumspect observer of animals, not a confident theorist of life.
Darwin was humble and modest in exactly the way that Inspector Columbo is. He knows from the beginning who thew guilty party is, and what the truth is, and would rather let the bad guys hang themselves out of arrogance and overconfidence, while he walks around in his raincoat, scratching his head and saying, "Oh, yeah--just one more thing about that six-thousand year old Earth, Reverend Snodgrass..." Darwin was a civil and courteous man, but he was also what is now polemically called a Darwinian fundamentalist. He knew that he was right, and that his being right meant that much else people wanted to believe was wrong. Design was just chance plus time, greed not a sin from the Devil but an inheritance from monkeys. "Our descent, then, is the origin of our evil passions!!" he wrote in his notebooks. "The Devil under form of Baboon is our grandfather!"
You don't achieve a triumph of this kind without knowning what you're doing, and Darwin was a cagey man when it came to carrying his day. He was pleased to let other men, particularly his great friend and champion T. H. Huxley, do the dirty work of polemics. Throughout thirty years of friendship, he and Huxley played, knowingly, a kind of good-cop, bad-cop game in public. Their correspondance shows that each knew his given role--when Darwin at last was put forward for an honorary degree at Oxford by the reactionary Lord Salisbury, it was with the severe corrollary that Huxley could not get the same. Huxley and Darwin, sharing the same basic views, enjoyed the joke. When Huxley had his famous debate with Bishop Wilberforce, Darwin kept silent, safe in the country, but wrote to his defender, "How durst you attack a live Bishop in that fashion? I am quite ashamed of you! Have you no reverence for fine lawn sleeves?"

The Worst Driving 2006 World Cup   posted by dobeln @ 10/22/2006 10:20:00 AM

Traffic is a major killer all around the world. Still, some places have a worse reputation than others when it comes to reckless driving. Luckily, a new study goes beyond mere prejudice in detailing how accident prone various immigrant groups are here in good ol' Sweden.

Short version: The Middle East and North Africa take the trophy this year by far. African males are almost competitive, but African women hold them back by being among the safest drivers around (even when adjusting for the number of driver's licences they hold).

And for those who want to see how their group stacks up, here are the key findings from the Swedish National Road and Transport Research Institute (rolls off your tongue nicely...):

Click the image for a more readable version.

You can find the entire report (in English) with plenty of tables and OLS goodness here.

Regulatory change in autism   posted by JP @ 10/22/2006 09:05:00 AM

The twin concordance rate in autism is something like 90% for monozygotic twins and 5% for dizygotic twins. This suggests a signigicant role for genetics in the development of autism. A new study identifies one of the possible genetic contributors, a regulatory change in the MET gene. MET signaling is important in a number of tissues, which the authors suggest is support for this being a valid finding. I'm pretty convinced--there's a replication study, and the authors don't do any funny things with statistics to make associations appear where they shouldn't.

Further, the variant they identify is in the promoter of the gene, and they show that, in vitro, it leads to reduced transcription factor binding and reduced transcription. This, of course, is the most presuasive evidence.

Given the hypotheses that posit epigenetic modifications in autism, it would be interesting to see what the methylation patterns are like in the region. In fact, the SNP is a C-->G change, which creates a CpG dinucleotide, a possible target for methylation.


Saturday, October 21, 2006

Sean Carroll's new book....   posted by Razib @ 10/21/2006 12:05:00 AM

Mr. (Dr.?) Evo-Devo, Sean Carroll, has a new book out, The Making of the Fittest: DNA and the Ultimate Forensic Record of Evolution. He gave an interview to NPR today, and he seems to be attempting to market this as an attempt to educate the public about evolution via applied genomics (e.g., DNA tests, etc.). Interestingly, Carroll points to the power of human evolution and local adaptation, though he used the canonical malaria resistence example rather than something more exotic. I've bandied about the idea that a "bottom up" DNA sequence-centric conception of evolution is the way to go in convincing the "skeptics." My general point was that macroevolution is simply intuitively unappealing to many because of the human tendency to essentialize species concepts. On the other hand if you start from DNA, something tangible which people can concede is substantive and real, and work the logic of mutation, migration, selection and drift, you can slowly box people in and work them up to agreeing that macroevolution naturally emerges from the microevolutionary axioms which are rock-solid. That being said, that's the theory, and this model is requires a particular intellectual level which I don't think applies to most humans.

Addendum: On a radio related note, check out this interview with a writer who covers game theory, quite a bit of time spent on J.M. Smith's work in the 1970s.

Friday, October 20, 2006

The veil   posted by Razib @ 10/20/2006 09:35:00 PM

Mickey Kaus and Robert Wright addressed the issue of veils over on Bloggingheads.tv. Mickey dismissed the idea that there is something substantive to the charge that it is important to see someone's face to facilitate communication. I was hopeful that Robert Wright, who knows something about evolution and psychology, would disagree, but Wright seemed to go along with this though I got the feeling from his voice and facial expression (ironically) that in his gut he didn't totally agree with what he was saying. On my other blog I asserted that the reality is that veiling is instinctively disturbing because faces are how we perceive other humans as individuals. Expressions convey essential information. Intellectually we all know that the seat of our consciousness lay in the functioning of our brains, but when we think of our loved ones, our friends, a famous celebrity, we fixate on their face as the token of who they are as individuals. Humans have a gestalt capacity to recongize, differentiate and interpret faces. This is an evolutionary adaptation, and can be lost through specific brain damage. Anthropologically humans have ornamented their face, covered or styled their hair, and so on, but it seems to me that veiling the face habitually is rare. It emerges in a specific sociopolitical context, veiling and obscuring of females and the shielding of their individuality in the public space seems to be a feature of extremely socially stratified societies characterized by patrilineages able to accrue wealth and power. Some Muslim commentators have pointed out that in fact the veil might have been adopted by Muslims from highborn Byzantines and Persians. It was a token of the civilization of the new Muslim elites that they treated their women the way that the Greek and Persian elites they superseded had (they also adopted the court ritual and motifs of the Byzantines and Persians). In India when the Muslims came and conquered high caste Hindus also adopted some of the same practices, including purdah (segregation and isolation of elite females).

When I listened to this BBC Special on the veiling controversy I was struck by the nature of some of the women who veiled themselves: they were not fundamentally socially isolated, and some of them even practiced professions. This is interesting to me because obviously the rise of veiling in civilized Eurasia was not correlated with the rise in status of women, rather, the spread of complex civilization was generally accompanied by a decline in the status of women (even ancient Egypt and Sumeria had more property rights for women than the later Eurasian civilizations). And yet here it seemed that some of these young Muslim women were taking up the veil as an assertion of their individual identity, that is, fundamentally it was a matter of female empowerment. Now, on one level I do agree that veiling is empowering, my own minimal but non-trivial experience with veiled women is that having someone see your face and expression while you are denied the similar privilege puts you in a disadvantageous position. And yet the symbolism of it all seems more important, and I was struck with the thought that this is a case of phylogenetic constraint due to cultural history. That is, as women liberate themselves in the modern West in any given cultural matrix they co-opt and adopt prior motifs and forms in their own culture and reshape and reinterpret them. For young Muslim women a transnational tendency toward modest dress and veiling in the extreme circumstances is a possibility because it is an acceptable and normal part of the range of variation within their culture. But, its origins were fundamentally connected with the control of elite women by high status males in civilizations where communitarian principles and coalitions of males were dominant. An analogy might be with the rise of "feminist theology," which seems to emerge (in my eye) from the reality that "progressive" men and women simply wish to hold onto what is fundamentally a patriarchal tribal religion and yet still espouse universal liberalism as a basic truth of the universe.

Update: Via Pickled Politics, I found this article:
Until only a few months ago, mainstream British politicians were extremely cautious about articulating the fears and resentments felt by many ordinary people on the subject of mass immigration.

Those who spoke out publicly (Enoch Powell's 'rivers of blood' speech is the notorious example) were ostracised. Political parties which raised the issue were thrust beyond the outer margins of debate the fate of the National Front and the BNP.

This self-restraint has now vanished. Practically every day for the past two weeks, another minister has insulted the customs, habits or religious beliefs of Britain's Muslim minority.

1) I have suggested before that the European Left's alliance with Muslims was purely tactical, and Muslims better be careful in assuming that the "sensitive" allies who winked at and enabled their lack of assimilation would back them on principle as opposed to expedience.

2) I think it is totally acceptable for beliefs & customs to be mocked. In particular, some of the customs of Muslims are at sharp variance with British norms. There is no such thing as a "multicultural utopia," now that Muslims aren't marginalia the real war stats.

3) I am heartened by this, even if it is an electoral strategy by "New Labor." The probability that Muslims will be rounded up in extermination camps is very, very, very low. I think the hysteria is over-wrought, and European elites better wake and stop playing PC-politics. The end is nigh, God willing (I have relatives in England who are Muslims for the record).

Thursday, October 19, 2006

Memory-associated SNP   posted by Coffee Mug @ 10/19/2006 11:05:00 PM

Fly pointed out this paper in the new issue of Science. The "T allele" of the protein KIBRA is associated with performance on certain human episodic memory tasks first in a Swiss cohort and then in two other populations controlling for attention effects and stratification effects. The "good memory" allele frequency varies across populations: Asian (75%) > African (~50%) > European (25%). fMRI during a memory task showed higher activation in the hippocampus and other related memory structures in people with the "bad memory" allele, suggesting that the memory structures were having to work harder or more inefficiently to encode the information. So far KIBRA is known to interact with dendrin, protein kinase C zeta, and protein kinase m zeta. You may recognize the name PKM zeta from a science paper a few weeks ago implicating PKM zeta in memory maintenance. I don't know what dendrin does yet. The initial SNP discovered is in an intron and doesn't seem likely to affect function, but there are other polymorphisms really close by, in neigboring exons, that are also significantly associated with the memory phenotype. It will be interesting to see in which part of the KIBRA protein these differences lie.

Republican & Democrat, rich & poor   posted by Razib @ 10/19/2006 09:16:00 PM

Chris comments on a paper which analyzes how income affects voting nationwide. Here's the conclusion:
In poor states, poor people vote Democrat and wealthy people vote Republican. The same is true in a medium-income state, though less so than in the poor state. In the wealthy state, however, income has very little effect on voting: both the rich and the poor vote Democrat and Republican.

Actually, I noticed this tendency in exit poll data years ago. Cultural issues become salient when basic needs are met I suppose?

Fast and slow spine dynamix   posted by Coffee Mug @ 10/19/2006 08:50:00 PM

Shame I gotta do white labels to keep my life stable. - Common

I checked out a couple sets of posters dealing with spine dynamics at SFN. One bundle from the Hayashi lab showed that the beta subunit of CaMKII serves an actin bundling role in dendritic spines. Get used to hearing about CaMKII. It makes up two percent of brain protein and has several interesting properties that make it intriguing as a memory-related signaling molecule. CaMKII at the synapse takes the form of 12-subunit donut-like structures (two interlocked 6-subunit structures). There is a family of CaMKII subunits. I don't know all of their properites, but CaMKII alpha is the one everyone usually concentrates on because it is synthesized following activity and has these nifty self-activating features that might make it good for maintaining a synaptic biochemical state. CaMKII beta is the boring wallflower subunit, but Hayashi may now have given it a chance to shine. They showed that actin polymerization (forming into long chains or scaffolds that provide structure for the spine) causes more beta-CaMKII to show up in dendritic spines. Dendritic spines are little knobs that stick off of dendrites where most excitatory synapses occur (here's some pics). The beta subunit slows down the actin dynamics responsible for spines wobbling around. Wobbling around is immature behavior for a spine, indicative of a weak synapse or perhaps searching for a new synaptic connection. Experimental reduction of beta CaMKII makes spines look more like filopodia, long, thin, wobbly growths off the dendrite (presumed to be the intial stages of spine formation). Expressing the beta-CaMKII binding domain can rescue this phenotype and make the spines look more stable and mature. Hayashi suggest a model in which initially actin is bundled in a fairly weak spine. Activity can destablize this bundling and allow the spine to wobble some and perhaps rearrange the post-synaptic protein formation. This might be mediated by increasing the alpha subunit content. I'm forming an alpha=unstable, beta=stable dichotomy in my mind right now. After the activity-induced destabilization, more beta-CaMKII can come in and re-stabilize/re-bundle the actin filaments in a new (maybe stronger) configuration.

Sutton and Schuman had some posters continuing their examination of synaptic homeostasis and mini EPSPs (excitatory post-synaptic potentials). Refresher: minis are caused by spontaneous neurotransmitter release even when there is no activity driving action potentials. We know from previous work that blocking minis can cause synapses to start inserting new receptors and grow in strength. In one poster they used a GFP flanked by the regulatory elements of the alpha-CaMKII mRNA to assay a certain signaling pathway's role in mini-mediated dendritic protein synthesis regulation. The experimental techniques get convoluted quickly because every manipulation involves inhibition of two processes to discover the effect of one. I'll skip those, you are welcome. In general they found that minis tend to increase phosphorylation of eEF2 and that action potentials tend to decrease the same. eEF2 phosphorylation is thought to decrease global translation during the elongation step. I mentioned it a couple weeks ago in reference to alpha-CaMKII synthesis as one of those counterintuitive regulatory paths in which turning down translation increases certain genes. Sutton and Schuman didn't find anything like that. Phospho-eEF2 (and thus minis) was associated with suppression of the reporter signal. Inhibiting the kinase that phosphorylates eEF2 (something that action potentials, non-spontaneous activity, might do) led to more protein synthesis and more reporter signal. Sutton didn't seem overly concerned that the direction of regulation for alpha CaMKII was opposite to that reported in Scheetz et al. They focused more on the idea that it is relatively uncommon to think of translation being regulated at the elongation step instead of the initiation step. I'll give'em that, but I thought the Scheetz story was cool, so I wish they would examine it a little more closely.

The other poster from Sutton and Schuman examined fast and slow spine dynamics in relation to minis and action potentials. We are now getting a dichotomy between minis and action potentials as stabilizing and destabilizing forces respectively. Fast dynamics was defined as movement of the spine during a 5 minute monitoring window. Slow dynamics usually involved spine growth (in the more stable widening of the head and neck manner) over about an hour or two. Minis tended to reduce fast dynamics and increase spine growth (slow dynamics) and action potentials did the opposite. Blocking minis or action potentials over an extended period of time produced effects on not just the size and shape of individual spines but also on the number of spines period. Initially letting minis run wild led to an increase in spine number, but over days this dropped off below baseline. The effect of action potentials appers to be to initially drop off the number of spines and then stabilize, maybe as neurons are adapting to the new higher activity level. Everything I have written has to be taken with the caveat that you can't actually isolate the effect of action potentials. All of the effects attributed to action potentials are really taken from experiments blocking the effect of minis AND action potentials at the same time, basically blocking any neural signals at all. The effects I attributed to minis are more directly related to actually looking at the different response between neurons with minis and without.

So with just a few posters we can build up a couple categories: stabilizing forces versus destabilizing forces.
  • Stabilizing: miniEPSPs, beta CaMKII, actin polymerization, eEF2 phosphorylation, inhibition of translation at the elongation step, inhibition of global protein synthesis.
  • Destabilizing: activity, action potentials, alpha CAMKII, protein synthesis upregulation
I'm thinking that memory may be encoded by passing through a destabilizing phase to a new, stronger stabilized phase. This would allow an interesting explanation for the phenomenon of reconsolidation. Reconsolidaton is complicated and a matter of debate, so keep in mind that the story is more complicated that I will present it now. Reconsolidation is demonstrated by allowing an animal to retrieve an established memory and then performing some manipulation to screw with their memory consolidation capabilities. For instance, you can give a strong electric shock or certain drugs. The animal then seems to have forgotten that particular reactivated memory in subsequent testing. Maybe the initial destabilizing force of synaptic activity for those memories allows a window of time when, if the pattern of activity becomes erratic, the memory will not be put back together right during the stabilizing phase.

Associative neurons in the amygdala   posted by Coffee Mug @ 10/19/2006 07:36:00 AM

The Devil sat behind me on the plane the night before last. I tried blogging from SFN last year. It is a silly idea. I will SFN blog after the fact from now on. One of the most remarkable posters I saw this week was from the Ledoux lab. The amygdala is one of the clearest cases for showing a particular memory trace in a structure (conditioned fear). The poster examined a protein marker for activation/plasticity one hour after training in either paired or unpaired tone-fear conditioning. This means that the animals all received the same amount of all stimuli, but the paired group received the tone just prior to shock which is the condition necessary to produce an association.They used a statistical technique called stereotypy to look for patterns of neuronal activation in the amygdala. There were more marked neurons in paired vs unpaired animals, but the more remarkable thing is that it appears to be the same neurons across animals (for 6 animals). Meaning that there may be a neuron that we can name (P1 or P2 were names they were using) whose hardwired function is to handle association between that particular tone and shock. Yes, I realize that this is probably not what it is "hardwired" to do, but you get the point. Part of the case for calling these the same neurons is that P1 (and others) has the same orientation, dendrite outgrowth, and position across animals. They are currently doing electrophysiology to strengthen the case. There are a subset of neurons that are activated with pairing, but not with unpaired conditioning that are being referred to as AANs (Associatively Activated Neurons? I think that's right.) As far as I could see there wasn't any particular anatomical locus you could stuff them in. They looked sort of like Cassiopeia if I remember correctly.

Fisher and Wright on Population Size: Part 2   posted by DavidB @ 10/19/2006 02:13:00 AM

Rather later than intended, here is Part 2 of this note.

Part 1 looked at R. A. Fisher's views on the effective population size of species before the publication of The Genetical Theory of Natural Selection (GTNS) in 1930. The main conclusion was that from an early date (1921) Fisher believed that there was usually enough migration between different parts of a species' range, on an evolutionary timescale, to neutralise the effect of genetic drift in causing gene frequencies in different parts of the species to diverge. Fisher therefore thought that for most purposes in population genetics a species could legitimately be treated as a single randomly interbreeding population. He did not hold the absurd view, sometimes attributed to him, that a species was literally random-breeding (panmictic) throughout its range, no matter how extensive that might be.

I said I would come back in the next instalment to consider Fisher's views in GTNS itself...

There is nothing in GTNS [1] to suggest that Fisher's views on effective population size had changed. The main novelty is that GTNS contains, in its chapter on sexual reproduction, a brief but important discussion on the nature of species and the process of speciation. But even these points had been foreshadowed in Fisher's correspondence.

First I will gather together those passages I can find in GTNS giving Fisher's views on the actual size of species. The first relevant passage, quite early in the book, is a remark that 'the number of individuals surviving to reproduce in each generation must in most species exceed a million, and in many is at least a million-fold greater...' [1, p10]

In the second (1958) edition of GTNS Fisher added an important comment shortly after this:

The circumstance that smaller numbers, even less than 100, are sometimes found to reproduce themselves locally, does not, as has been supposed, add to the frequency of random extinction [of genes], or to the importance of the so-called 'genetic drift'. For this, perfect isolation is required over a number of generations equally numerous with the population isolated. Even if perfect isolation could be postulated, which is always questionable, it is still improbable that the small isolated population would not ordinarily die out altogether before a period of evolutionary significance could elapse, or that it would not be later absorbed in other populations with a different genetic constitution.[1, p.273, Dover p.10]

This was a point he had made in correspondence to both Leonard Darwin and Sewall Wright in 1929 - and apparently accepted by Wright at that time - but which Fisher unfortunately did not make explicitly in the first edition of GTNS. If he had, the 'Fisher-Wright debate' might have been better understood. Note particularly that Fisher's objection is not just concerned with steady small-scale migration, but also with occasional larger changes. On a time scale of thousands of years, we cannot expect climate and topography be constant: ponds dry up; rivers change their course; and changes in temperature and rainfall involve changes in vegetation and the associated animal species.

Another addition in 1958 is explicitly aimed at Sewall Wright, who had studied the genetics of the rare plant species Oenothera organensis. Fisher comments thus:

In the case of Oenothera organensis the existing wild population has been thought to be so small as one thousand individuals... Species having populations of less than 10,000 must, of course, be presumed to have fallen greatly in population during their recent evolutionary history... Sewall Wright has proposed that the number of alleles observed might be the sum of the number of alleles in different highly isolated groups into which the totality of this small population is divided. This should be the case if the larger population has in its recent history been subdivided. Isolation, however, of the degree required, if it now exists, would necessarily be a recent condition due doubtless to the recent large reduction in population numbers.[1, p.294-6, Dover p.109]

Returning to the first edition text, we have found a clear statement that a species population is usually greater than a million, and a somewhat less clear statement that it is often 'at least a million-fold greater'. A 'million-fold greater' does not mean 'a million greater' but literally a million times greater - that is, at least a million million! It might be supposed that Fisher was here writing carelessly, but several later passages show that he did believe some species had populations of a million million, while populations of over a thousand million were commonplace. For example, In chapter 4 he discusses the choice of a suitable scale for measuring gene ratios, and advocates a logarithmic scale:

The range of possible frequency ratios on the logarithmic scale thus depends on the number of individuals in the species, and it is easy to see that it is increased by 2log10, or 4.6, if the population in the species is increased tenfold. For example, a species of 10,000,000,000 individuals will give a range of values from about -23.7 to +23.7.[1, p72, Dover p.79]

He goes on to recommend that the population size should be counted when individuals are reaching sexual maturity, and at the lowest point of any annual cycle: 'we shall count each generation near the maximum of its reproductive value, and when its numbers are least'. [1, p73, Dover p.80] Evidently, then, Fisher is not thinking of his populations of many millions as just gametes or fertilised eggs, most of which will die before maturity. Later in the chapter he refers to 'a species in which 1,000,000,000 come in every generation to maturity'[1, p78, Dover p.85], and to 'a mutant form [existing] in as many as 1,000 million individuals in each generation'[1, p79, Dover p.80]. He develops equations to deal with the effects of mutation and genetic drift, in which n is 'the number of individuals breeding in each generation', 'a large number of many millions or thousands of millions'[1, p84, Dover p.91]. To show the range of possible effects, he calculates the effect of taking values of n 'from a million to a billion'[1, p91, Dover p.98]. In American usage, and in recent British usage, a billion means a thousand million: 1,000,000,000 or 10^9. But in Fisher's day the usual British practice was to use a billion for a million million, or 10^12. To remove any doubt on this point, Fisher's table includes values from 10^6 to 10^12: from a million to a (traditional British) billion. Finally, at the end of the chapter he refers again explicitly to 'a population of a thousand million or a billion individuals'[1, p96, Dover p.103].

It may be wondered where Fisher acquired these views on the size of species, and whether they were generally accepted in his time, but I don't know the answer to this. It may be more interesting to consider whether they are (or were) correct.

A usual lower limit of one million for the total population of a species does not seem unreasonable. With the exception of species endemic to oceanic islands, deep lakes, and other special cases, we would expect most species, unless they are close to extinction, to have a geographical range of at least one million square kilometres. This may sound a lot, but it is less than 1 percent of the land area of the planet. For comparison, the smallest continent, Australia, has an area of about 8 million square kilometres. Most species, with the stated exceptions, range over a substantial fraction of a continent, or an equivalent part of the oceans. With a range of one million square kilometres a species population of 1 million would therefore require only an average density of 1 mature individual per sq. km., though not necessarily spread evenly and continuously across that range For most species of animals and plants this seems plausible. The main exceptions would be large mobile predators like lions or eagles, which may require a hunting range of 10 or more sq. km. to find enough prey. In modern times many large mammals have populations of less than one million, but this is usually due to hunting and destruction of their habitat by man. In natural conditions, subject to the stated exceptions, Fisher's lower limit seems reasonable.

There might well be some incredulity about the upper end of the range. I have seen it suggested (but unfortunately cannot recall where) that Fisher's figure of 10^12 was not intended literally, but only as a theoretical illustration of his population-genetics model. I doubt this: the statement that 'the number of individuals surviving to reproduce in each generation must in most species exceed a million, and in many is at least a million-fold greater' appears quite literal. But is it in fact impossible? Certainly one would not expect any vertebrate species to have a population of a million million. Man has a population of over 6 thousand million, and several domesticated species (cow, sheep, pig, dog, cat) have populations of one or a few thousand million. I hazard a guess that the most numerous land vertebrate is the domestic chicken, with an estimated world population of 23 thousand million. The total world population of small rodents may well exceed 100 thousand million, but this is divided among many species. Some widespread bird species may also run to thousands of millions. In the sea, when not over-fished by man, some species of fish have very large populations. A type of sardine migrates in vast shoals along the coast of South Africa. A single shoal has been measured at 40 km. long by 15 km. wide and 40 metres deep, giving it a volume of 2,400 million cubic metres. It would therefore only take a density of 10 sardines per cubic metre for a single shoal to outnumber the world population of the chicken.

Still, none of these figures come close to a million million. However, most animal species are not vertebrates, but small invertebrates. (Plants raise different issues: individuals are generally quite large but, as autotrophs, capable of high population densities.) A population of a million million would require an average density of one mature individual per square metre over 1 million sq. km., or a lower density over an appropriate larger area. For many insects and other small invertebrates this seems quite achievable. Very small insects like thrips and aphids can have immense populations. A single infestation of alfalfa aphids was once estimated at 170,000 million in an area of a few hundred square kilometres. [2, p. 266] For more typical examples, in the 1920s the agricultural research centre at Rothamsted in England carried out regular sample censuses of the invertebrates in the soil, and estimated that there were around 800,000 earthworms, nearly three million hymenoptera, one and a half million flies, and two and a third million springtails (small primitive insects) per acre of arable land (about 4000 sq. m.), giving a density of nearly 2,000 of these creatures per square metre.[3, p.107] (Of course, these would not all be breeding adults, and they would be divided among many species.) Fisher was the chief statistician at Rothamsted, so he would have been aware of these vast numbers of small invertebrates. And all this is without counting nematodes and other microscopic creatures. Provided we set aside our preoccupation with large vertebrates, a species population of a million million is by no means impossible.

Of course, as Fisher recognised, for some purposes what counts is the population of breeding adults at its lowest point. (Technically, the effective population size is somewhat larger than this, but we need not go into this.) It may therefore be pointed out (as Sewall Wright did) that many populations are subject to large fluctuations. This is true, but its significance should not be overstated. Given the assumption of free migration within a species, what matters is not the local population size but the global population, and this is likely to be less variable, as local fluctuations often cancel out. Many species also have adaptations for avoiding or resisting severe conditions, such as migration, or producing resistant eggs, larvae, or pupae. The adults of many insect species die out in the winter, but the population is preserved by eggs or larvae in sheltered places.

Overall, Fisher seems justified in assuming that total populations of most species run to millions, if not many millions. This is important in Fisher's view of evolution for two main reasons. First, the relative impact of selection and genetic drift on an allele depends on the numbers of the allele in the population, which are constrained by the population size. The change in numbers due to selection on an allele is proportional to the number of copies of the allele in the population at the time. In contrast the change in numbers due to genetic drift, in each generation, is closer to the square root of the number of copies of an allele, so it increases more slowly than the number of copies. If the number of copies is very small, as in the case of a single new mutation, genetic drift is almost always more important, until by chance the number has drifted to a high enough level for selection to become the predominant influence. If the population itself is very small (of the order of a few thousand) this point may never be reached. And if the selective advantage of the allele is very small (say, less than 1 in a million), very large populations are needed if the selective advantage is not to be swamped by drift. This is relevant, as Fisher saw, to his theory of the evolution of dominance, which requires very weak selection operating over long periods.

The second major implication is for the effect of mutation rates. A mutation which only ever occurs once in a species is very likely to be lost by chance before it can establish itself, even if it has a substantial selective advantage. If on the other hand it recurs on many occasions, it has a high probability of eventually by chance reaching the level at which selection becomes the predominant influence. The frequency with which the mutation recurs depends on the mutation rate and the population size. If the mutation rate is reasonably high - say 1 in 100,000 per generation - it will recur frequently (over an evolutionary timescale of thousands of generations) even in small populations. But if the mutation rate is very low, it may not recur at all unless the population is large. Fisher believed that extremely rare mutations might play a significant part in long term evolution, and for this reason believed that adaptive evolution would progress faster in large populations.

Fisher's conclusions however all presuppose that there is sufficient migration and interbreeding among different parts of a species, over an evolutionary time scale, to offset the effects of genetic drift in causing local gene frequencies to diverge. It is therefore disappointing that GTNS contains no explicit, quantified discussion of the effects of migration, other than the brief passage added at page 10 of the Dover edition. GTNS does however contain a very interesting discussion of the nature of species, in the chapter on sexual reproduction:

The intimate manner in which the whole body of individuals of a single species are bound together by sexual reproduction has been lost sight of by some writers. Apart from the intervention of geographical barriers so recently that the races separated are not yet regarded as specifically distinct, the ancestry of each single individual, if carried back only a hundred generations, must embrace practically all of the earlier period who have contributed appreciably to the ancestry of the present population. If we carry the survey back for 200, 1,000, or 10,000 generations, which are relatively short periods in the history of most species, it is evident that the community of ancestry must be even more complete... In sexual organisms... each individual is not the final member of a single series, but of converging lines of descent which ramify comparatively rapidly throughout the entire specific group. The variations which exist within a species are like the differences in colour between different threads which have crossed and recrossed each other a thousand times in the weaving a single uniform fabric.

The effective identity of the remote ancestry of all existing members of a single sexual species may be seen in a another way, which in particular cases should be capable of some quantitative refinement. Of the heritable variance in any character in each generation a portion is due to the hereditary differences in their parents [i.e. the differences between the parents of different individuals] , while the remainder, including nearly all differences between whole brothers and sisters, is due to genetic segregation. Those portions are not very unequal; the correlations observed in human statistics show that segregation must account for a little more than two-fifths, and the hereditary differences of the parents for nearly three-fifths of the whole. These hereditary differences are in their turn, if we go back a second generation, due partly to segregation and partly to hereditary differences in the grandparents. As we look farther and farther back, the proportion of the existing variance ascribable to differences of ancestry becomes rapidly smaller and smaller; taking the fraction due to segregation as only 2/5 in each generation, the fraction due to differences of ancestry 10 generations back is only about one part in 100 while at 30 generations it is less than one in four millions.[1, p124-5, Dover p.138-9]

It is noteworthy here that Fisher is implicitly using the extent of interbreeding as the criterion for species identity, as in the 'biological species definition' of Ernst Mayr, though Mayr had not yet promulgated this when Fisher was writing (1930). Fisher's application of the 'analysis of variance' to the subject is also interesting, and deserves to be evaluated by a competent statistician (i.e. not me). There seems to be an assumption that the 'ramification' of ancestry is unlimited and uniform however far back we go, until it embraces the entire species. This will often be the case, but if, say, an individual is from a small, relatively isolated village, we might suppose that his ancestry would ramify more slowly if we go back more than a few generations. On a larger scale, we might wonder how Fisher would account for the differences between geographical races. In fact, Fisher goes on to say:

It is only the geographical and other barriers to sexual intercourse between different races, factors admittedly similar to those which condition the development of incipient species as geographical races, which prevent the whole of mankind from having had, apart from the last thousand years, a practically identical ancestry. The ancestry of members of the same nation can differ little beyond the last 500 years; at 2,000 years the only differences that would seem to remain would be those between different ethnographic races; these, or at least some of the elements of these, may indeed be extremely ancient; but this would only be the case if for long ages the diffusion of blood between the separated groups was almost non-existent.

In the next section of the chapter, Fisher gives a brief but important dicussion of speciation, of which it has been said: 'Had Fisher developed any of his ideas mathematically the history of speciation might have been quite different' [4, p.7]. But there is still no quantitative treatment of the effects of migration to justify Fisher's confidence that a species can usually be treated as a single interbreeding population. For such a treatment we must turn to the writings of Sewall Wright. Part 3 of this note, if and when I get round to it, will therefore look at Wright's work on the subject.


[1] I will give page references to The Genetical Theory of Natural Selection: a Complete Variorum Edition, ed. J. H. Bennett, 1999, and, for convenience, to the more widely accessible Dover edition. (Where only one page reference is given, it is the same in both editions.)

[2] H. Andrewartha and L. Birch: The Ecological Web, 1984.

[3] Charles Elton: Animal Ecology, 1927, quoted from the Methuen Paperback edition.

[4] S. Berlocher, in Endless Forms: Species and Speciation (ed. D. Howard and S. Berlocher), 1998.

Wednesday, October 18, 2006

Stasis   posted by gcochran @ 10/18/2006 02:39:00 PM

A lot of people seem to have the idea that significant human biological evolution stopped when we became behaviorally modern. I'm wondering just how they got that idea. Can anyone give me some examples of influential instances of this claim? Influential papers, texts, popular books, bubble gum wrappers, etc etc

Tuesday, October 17, 2006

Sunni vs. Shia (again)   posted by Razib @ 10/17/2006 06:11:00 PM

By now most of you have read The New York Times piece about the inability of some government officials and representatives to distinguish between Sunni & Shia Muslims. I can't say I'm that surprised. Steve Sailer has been saying for years the phonetic similarity is probably part of the problem. There are two major issues:

1) The substantive theological differences between Sunnis and Shias, and within Sunnis and Shias.

2) The distribution of the two groups.

If you don't know 2, click this map before reading on (this map is a general guidline, there are errors in it which I will point out below).

Who is Shia and who is Sunni isn't as simple as one might think. Consider that the map above labels Oman a Sunni nation, but it isn't, it is an alternative stream of Islam. Why does this matter? Well, if you assume that Oman is Sunni, and Saudi Arabia and Iran are looking to gain influence, one might assume Oman will automatically lean toward Saudi Arabia. The map is also fallacious insofar as Yemen has a significant Shia minority, but, these Shia are very similar to Sunnis in the spectrum of difference (e.g., the distance between Sunni and Ismaili is greater than Sunni between Twelver is greater than between Sunni and Zaydi). John Walker Lindh for example was confused when he went to Yemen and he wanted to go find a mosque to pray in where there were only Sunnis...when in Yemen Sunnis and Shia often pray together. Syria is dominated by a group called Alawites, who are sometimes defined as Shia. In fact, the clerics of the largest branch of Shia, the Twelvers (they dominate Iran, Iran, Lebanon and the Gulf) have recently recognized the Alawites as Twelvers. They aren't, this is a political move to give the Alawites more legitimacy in the eyes of the Sunni majority who they rule (Iran has traditionally allied with Syria in the games of geopolitics). In Turkey there is a related minority, also often defined as Shia, termed the Alevi, who though technically Shia are also rather peculiar in their beliefs. I point out this minutiae because if you are going to get involved in the Byzantine politics of the Middle East, and offer opinions (which seems the main role of the blogosphere right now), you had better have a excellent mastery of the background details. Analysis based on a shaky grasp of the facts is useless (there are obviously differences within Sunni Islam, but not as much in my opinion because "Shia" is often simply a catchall term for various groups which have left the mainstream for various reasons).

Which brings me to a second point:
"It's a difference in their fundamental religious beliefs. The Sunni are more radical than the Shia. Or vice versa. But I think it's the Sunnis who're more radical than the Shia."

This perception that the "Shia" or "Sunni" are more radical is problematic and leads to confused heuristics. I myself as a child had the opinion that the Shia must be more radical, or fundamentalist, because of the nature of Iran. This is not true. In Syria and Turkey the "Shia" are bulwarks of the secular regime (in Turkey though they tend to support the secularist project). In Iraq the Shia have traditionally been part of the religious opposition, but they have also been dominant within the Communist party. In Pakistan the Shia tend to support the more secular party headed (traditionally) by the Bhutto family ( according to Vali Nasr the Bhuttos are a Shia family, while the founder of Pakistan was born into a Shia family). Which group is more theocratic and radical? That depends, a think a real rule of thumb is that the group prone to theocratic tendencies in a given country will be the group in the majority. In Iran Shia are 90% of the population, so they are theocratic. In Syria, Turkey and Pakistan they are a minority, so they tend to support separation of mosque (which will be Sunni dominated) and state. What is contextual is interpreted as intrinsic, but if one knows the distribution of Shia and their role in various nations, and the same with Sunni, one sees that the heuristic that one or the other is more "radical" is very flawed and will result in incorrect predictions.

Of course, this isn't the sort of thing that is interesting to most people. It would obviously be best if government officials who played a role in making decisions where this knowledge would be critical would be aware of the details. But I'm not holding my breath, my own experience on this and other blogs is that when it comes to opinions about Islam and the Middle East research is deemed unnecessary and the empires of opinion conquer all (in fact, I have been told that knowing too much is an impediment to proper understanding, and though I accept this as true in some theoretically rigorous sciences where excessive acceptance of received wisdom blinds one to new findings and insights, foreign policy and such are it seems mostly empirical disciplines where a mass of facts exists without great theoretical scaffolding).

Multi-unit recording: SFN decompression   posted by Coffee Mug @ 10/17/2006 12:34:00 PM

Almost done with ATL and the Society for Neuroscience conference. To gel all this info in my head I'll try to write some of it down. A friend and I went to a short course on Friday organized by Gyorgy Buzsaki entitled, "Visualizing large-scale patterns of activity in the brain: optical and electrical signals." I am currently reading Buzsaki's book "Rhythms of the Brain" (recently reviewed in Science). Buzsaki is a leader in his field and is making substantial contributions to the understanding of electrical signals in the brain and the organization of neuronal assemblies. I recorded all the lectures on my cell, but somehow in the midst of lots of BootCamping have (i hope temporarily) fried my ability to establish a relationship via bluetooth. The upshot is that I will try to provide you with decent-quality audio of the lectures when I get organized again.

Buzsaki did the intro and the first talk, which is basically a reiteration of Cycle 3 in his new book. Here's the deal. Neurons produce electrical signals that correlate with stimuli and behavioral states. We would like to be able to speak this language so we can read neurons and know what they are talking about while an animal is awake and behaving. The possibility exists in the future of using this information to speak to neurons directly with electrical stimulation. Currently, the best way to listen to neurons is with extracellular unit recording. With this technique you mainly capture short large-amplitude changes in the potential difference across the neuronal membrane. Most of these are action potentials, in which positively-charged sodium rushes into the cell creating a negativity outside the cell near the cell body (soma, a current sink). It is becoming increasingly clear that to understand some very important brain functions we need to be able to do more than sample individual neurons. We need to be able to look at the covariation in the "noise" of single-unit firing. To do this you need contemporaneous recording from a large number of neurons. So techniques have been developed for inserting multiple extracellular electrodes into, say, a rat hippocampus, and analyzing the temporal relationships between firing patterns of individual neurons.

If you just put one electrode in, you can't tell whether all the spikes you record are coming from a unique source. That electrode might capture activity from ten neurons that you can't tell apart. For instance, if the electrode was placed directly in between two neurons with similar firing properties you might confuse them with one neuron that fires a whole lot. To get around this you need to triangulate using multiple recording sites close together with a known spatial configuration. Now neuron B will be slightly weaker than neuron A in electrode B, but both electrodes will pick up the signal and you can do math to figure out that neurons B and A are separate signals. Most of Buzsaki's talk was on refinements of this process because it is really really difficult to actually be sure you are uniquely identifying a unit. Action potential sizes and signatures change, especially during really interesting complex burst firing patterns. More recording sites buys you more information, but at the cost of tissue damage.

Most multi-unit recording is performed using "tetrodes" four small wires wrapped around each other to give you four recording sites near each other. They can be implanted in an array in the ballpark of 30-100 tetrodes. These are still very much in use and are producing some beautiful data. Buzsaki is developing an alternative: Micro-Electro-Mechanical System-based recoding devices. These are silicon probes created using the techniques established for creating microchips, integrate circuits, etc.. (I don't know how this works, I assume some of you do). These have the advantage of being thinner, producing less tissue damage, having more refined control over the spatial configuration of the recording surfaces, and allowing some on-chip processing (i.e. signal amplification).

I won't dazzle you with my poor understanding of the algorithms he is developing to sort out the unit isolation and identification problems. One of the major issues as far as I could tell is that extracellular potentials don't always come from the axon-hillock at the cell soma, but instead can be generated by activity spikes in the dendrites, so algorithms that treat units as a point-source miss the complexity of electrical signals coming from a ramified polar cell-type. Another issue is the classification of cell-types. You can begin to guess at an inhibitory connection when you see a spike from one unit followed almost immediately by decreased activity in a separate unit. Those sorts of things. There is incredible diversity especially in the inhibitory neuron population. Neurons can be classified in terms of spiking patterns and forms and the effect of their spikes on other neurons. This last classifier is only achievable using multi-unit techniques.

The book is recommended. I'll hit you back with the mp3s soon I hope. I have nothing to report about ATL. No playas playin, no ridin on them thangs.. Looks mostly like rainin on my thangs, like everyday.

Monday, October 16, 2006

Who da man?   posted by Razib @ 10/16/2006 09:37:00 PM

Frank Ryan: "Frank Beall Ryan, Ph.D. (born July 12, 1936) is a retired American football quarterback who played for the Los Angeles Rams (1958-1961), Cleveland Browns (1962-1968) and Washington Redskins (1969-1970). Although he led the Browns to their last National Football League title in 1964, Ryan is best remembered for being perhaps the only Ph.D. in mathematics to play in the league."

Related: 10 Beauties with Brains - Most Intelligent Actress.

Autism & genetics   posted by Razib @ 10/16/2006 09:01:00 PM

Mutated gene raises autism risk, US study finds:
People with two copies of the mutated gene [MET] have 2 to 2.5 times the normal risk of autism and people with one mutated copy have 1.7 times the risk, he said.
Levitt said the mutation does not change the function of the gene, but changes gene expression -- how active the gene is.

The study is going to be published in PNAS.


Mutants documentary torrent   posted by Razib @ 10/16/2006 07:10:00 PM

Torrent for Armand Leroi's Human Mutants.

Sunday, October 15, 2006

Why the regulatory changes vs. coding sequence changes debate is inane   posted by JP @ 10/15/2006 08:59:00 PM

According to the latest estimates, the common ancestor of humans and chimpanzees lived sometime around 5 million years ago. Since then, a lot has happened. Presumably, there has been plenty of change along the lineage leading to chimpanzees, but let's be honest-- from our point of view, a lot more has happened along our lineage. We have Shakespeare, Klimt, and the International Space Station; they jab sticks into anthills. The biological basis for this disparity is certainly a worthy line of inquiry. As a first step down this path, I assume most readers here will agree with me that invoking the hand of God, while awfully tempting, would be laughable. So let's turn our focus to a more profitable enterprise: genetics.

In the 1970s, the technology was a such a state that the proteins in the blood of both humans and chimps could be compared at some rough level. And as it turns out, we aren't that different after all. Or rather, we're less different than people expected to find, given that, as humans, we consider ourselves the Greatest. Species. Ever. So if our blood proteins aren't that different, what makes us human?

One possible answer was provided in 1975, in an influential paper by Mary-Claire King and Allan Wilson. In their own words:
We suggest that evolutionary changes in anatomy and way of life are more often based on changes in the mechanisms controlling the expression of genes than on sequence changes in proteins. We therefore propose that regulatory mutations account for the major biological differences between humans and chimpanzees
Of course, this hypothesis was based on very little data (as Bruce Lahn pointed out in his interview) -- the fact that human red blood cells and chimp red blood cells are almost the same doesn't really tell us that much. But at the time, people were apparently expecting radical differences between human and chimp proteins across the board, so this paper shifted some paradigms[1].

Now, 30 years later, it's possible to compare the genome sequences of the two species, and microarray technology makes it possible to compare gene expression levels as well. So are we close to settling this issue? My answer: hell no. And here's why:

Here's the question we're supposed to answer: which are more important-- protein-coding changes or regulatory changes? And here's the problem with that question: how do you define important? Let's make a list of the ways humans differ from chimpanzees-- we walk on two feet, we have bigger brains, we have less hair, etc. etc. You can add your own if you like. If a protein-coding change gives us the bigger brain, but a regulatory change the lack of hair, who wins? Sure, you could argue about which trait contributes more to some notion of "human-ness", but frankly, who gives a shit? Both are pretty important.

And in reality, any of those traits is likely to be influenced by a number of factors. In the developmental networks that have evolved seperately in the last 5 million years, the components of the networks (protin-coding changes) as well as the relationships between those components (regulatory changes) are both likely to have changed. So no single mutation is going to be the mutation. I feel like many people are under the impression there's going the equivalent of an SRY gene [2] that easily discriminates between chimps and humans. Ain't gonna happen.

So let's say someone is a true partisan on one side of this debate and wants to settle it once and for all. What would be necessary? Here's my list:
1. A catalogue of all the phenotypic difference between humans and chimps.
2. A list of all the genetic changes underlying these difference (classified as coding and regulatory, of course), and a weight assigned to each change accoring to its relative importance in the generation of the phenotype.
3. An objective measure of "human-ness" that assigns relative importance to each of the phenotypic differences.

And there you go. For the person that does this, I will buy a cold beer.

[1] King and Wilson also propose that point mutations may be less important than rearrangements like tranlocations and inversions in human evolution, but they present no data on this and no one really remembers this hypothesis anymore.

[2] In sex determination in humans, there's a single gene, SRY, that pretty much determines who's a male and who's a female (with, of course, the necessary caveats). In this case, it's clear-- take a female, add this gene, and you pretty much get a male. This protein-coding difference is arguably the most important difference between males and females.

Mendel's Garden #8   posted by Razib @ 10/15/2006 07:29:00 PM

Mendel's Garden #8 is up at Discovering Biology in a Digital World.

Saturday, October 14, 2006

Rod Dreher leaves Catholicism for Orthodoxy   posted by Razib @ 10/14/2006 04:02:00 PM

Rod Dreher has a long piece about how and why he left Roman Catholicism for Orthodoxy. As an observer of religion as a natural phenomenon I was fascinated by the various parameters which compelled him to make such a drastic change. Keeping in mind what I've said about theology in the past, I was particularly interested by this:
I had to admit that I had never seriously considered the case for Orthodoxy. Now I had to do that. And it was difficult poring through the arguments about papal primacy. I'll spare you the details, but I will say that I came to seriously doubt Rome's claims. Reading the accounts of the First Vatican Council, and how they arrived at the dogma of papal infallibility, was a shock to me: I realized that I simply couldn't believe the doctrine. And if that falls, it all falls. Of course I immediately set upon myself, doubting my thinking because doubting my motives. You're just trying to talk yourself into something, I thought. And truth to tell, there was a lot of that, I'm sure.

I tend to be of the opinion that intelligent believers accept the reasons to believe because they already believe. Faith makes reason compelling, reason does not lead to faith.

Update: Here is Rod Dreher's blog. The post in question has been removed, reedited, placed back, removed multiple times. You'll never known when it shows up. Since the comments are via haloscan that couldn't be the issue since it is an offsite server.

Heroes   posted by the @ 10/14/2006 12:08:00 AM

Heroes would be a cool show if they dropped the retarded voice-overs about "evolution".

Friday, October 13, 2006

Evolutionary forces in the (human) genome   posted by Razib @ 10/13/2006 12:01:00 AM

Apropos of the discussion below, Forces Shaping the Fastest Evolving Regions in the Human Genome, in PLOS GENETICS:
Studies of differences between the chimpanzee and human genomes have focused on protein-coding genes. However, examples of amino acid changes between chimp and human have not been able to explain most of the phenotypic differences between us and our fellow hominoids. King and Wilson (1975) proposed that the main differences between chimps and humans will be found in non-coding regulatory DNA. Consistent with this hypothesis, recent whole-genome scans for evolutionarily conserved DNA elements that have evolved rapidly since our divergence from the chimp-human ancestor have discovered largely non-coding regions. The authors investigate a carefully screened set of 202 such human accelerated regions (HARs). Most of these HARs do not code for proteins, but instead are located in introns and intergenic regions near protein-coding genes. The set of genes near HARs is enriched for transcription factors, suggesting that the HARs may play important roles in gene regulation. This study also discovers a striking adenine and thymine to guanine and cytosine bias among the human-specific changes in HARs. This suggests the involvement of biased gene conversion or a selective force to increase guanine and cytosine content. Some HARs may also have been under positive selection. Hence, there is likely more than one evolutionary force shaping the fastest evolving regions of the human genome.

Also, Functionality of Intergenic Transcription: An Evolutionary Comparison:
In order to convert the genetic information encoded in an organism's genomic sequence into the functional features, the genomic sequence must be transcribed. According to the current genome annotation, the human genome encodes 20,000–25,000 protein-coding transcripts and a smaller number of non-coding transcripts. There is, however, a growing body of evidence indicating that a much greater proportion of the human genome is transcribed than is accounted for by the existing annotation. Much of this evidence has been found using tiling arrays, microarrays that enable the measurement of transcription regardless of existing annotation. Although some have suggested that these transcripts represent previously unidentified functional RNAs as well as extensions of known genes, the extent of their functionality remains unknown. In this study, Khaitovich et al. assess the functionality of these novel transcripts by testing the extent to which their expression is conserved between humans and chimpanzees in different tissues. The results suggest that, surprisingly, the expression of both known and novel transcripts was affected by the same functional constraints during human and chimpanzee evolution.

Addendum from JP: For some thoughts on the first paper, see here and here. For some thoughts on the second, see here.

Thursday, October 12, 2006

The definitive Homo floresiensis post   posted by Razib @ 10/12/2006 01:39:00 AM

If you have haven't checked our Carl Zimmer's Homo floresiensis: Two Years Out, please do if you are curious about the topic. For me, the longer the "controversy" rages the less plausible I find that this could be a new "species."

Wednesday, October 11, 2006

More than monkey brains   posted by Razib @ 10/11/2006 11:18:00 PM

DNA trail points to human brain evolution:
A new study comparing the genomes of humans, chimps, monkeys and mice found an unexpectedly high degree of genetic difference in the human DNA regions that influence nerve cell adhesion, compared with the DNA of the other animals.

Accelerated evolution here allowed human brain cell connections to form with greater complexity, enabling us to grow bigger brains, the researchers suggest.

From the interview with Bruce Lahn:
2. Your work on genes involved in human brain evolution (i.e. ASPM and microcephalin) has focused on amino acid changes. It has been hypothesized that most of the differences between humans and chimps are due to regulatory changes. Do you feel this is still a viable hypothesis? Do you consider your work a challenge to this hypothesis?

The hypothesis that most human-chimp differences are due to regulatory changes is proposed in the absence of any data. So, I don't place too much weight on this hypothesis to begin with. Nevertheless, I acknowledge that this hypothesis has influenced the thinking of many people. Our work showed that coding region evolution is likely to be important for human brain evolution. In this regard, it can be considered to be a challenge to the hypothesis. However, our work by no means argues that regulatory changes are necessarily less important than coding changes. So, the jury is still out.

Drinking associated with risky sexual behavior   posted by JP @ 10/11/2006 07:15:00 PM

It's easy to make fun of studies like these, but hey, sometimes once you measure a phenomenon you find something unexpected. Not in this case, however:
Among men, heavy alcohol use was associated with higher odds of all risky sex outcomes examined, including unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32), multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR = 3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to 6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than both problem and heavy drinkers.

Asian hostility   posted by Razib @ 10/11/2006 12:39:00 AM

Publics of Asian Powers Hold Negative Views of One Another. Pakistanis dislike the United States more than India!

Tuesday, October 10, 2006

Global inhibition, specific activation   posted by Coffee Mug @ 10/10/2006 11:06:00 PM

Another aspect of the Raab-Graham et al. paper that might be missed in the flurry of different pharmacological agents and signaling pathways, is that the synthesis of Kv1.1 is actually increased in response to a manipulation that normally inhibits translation. Rapamycin is the drug of interest here. It inhibits a protein called mTOR (mammalian target of rapamycin). There is still some debate about what mTOR does exactly, but suffice it to say that it activates other signaling molecules downstream. The end result of mTOR signaling is to promote cap-dependent translation. Most mRNAs have a structure on the head end called a 5' cap. It is basically a nucleotide put on backwards, but it can be recognized by proteins involved in the initiation of protein synthesis. Recognition of the cap by these proteins is usually necessary to get the mRNA hooked up with the ribosomes. So rapamycin should be inhibiting this process and thus inhibiting translation initiation for most cellular mRNAs. Note that other protein synthesis inhibitors that act further downstream actually do decrease the rapamycin-induced increase in Kv1.1.

We don't get an explanation for this counter-intuitive regulation mechanism. The simplest explanation would be that Kv1.1 has an internal ribosomal entry site (IRES). IRESs are common in viral transcripts. Their mechanism is not fully understood, but they somehow allow ribosomes to jump in and bind mRNAs without having to deal with caps or cap-binding proteins. When cap-dependent translation is inhibited, cap-independent translation-capable transcripts would get all the goodies. RNAs with IRESs will be at an advantage. It is not unprecedented for important neuronal mRNAs to carry these elements. For instance, Pinkstaff et al. found functional IRESs in five dendritic mRNAs (including Arc and CaMKII). Unfortunately for this hypothesis, Raab-Graham et al. found no evidence for an IRES in Kv1.1 and showed that the 5' UTR (where IRESs usually hang out) was not necessary for the rapamycin regulation. This suggest that rapamycin is having its effect through some signaling pathway besides that responsible for cap-dependent translation.

Rather than dwell on Kv1.1 since we don't know the answer. I thought I'd show you a couple more examples where translation is inhibited, but certain RNAs do extremely well. I think the mRNA for CaMKII must contain every type of regulatory element, and must be controlled by every possible pathway. In this paper, Scheetz et al. used a fairly unusual in vitro preparation that should mostly just carry the synaptic compartments of dendrites to study the effects of NMDA receptor activation on protein synthesis. As you may know, the classic story is that when two neurons fire at the same time NMDA receptors are activated on the post-synaptic neuron allowing calcium into the cell and initiating signaling that will lead to plasticity. Scheetz et al. found that in the first two minutes following NMDAR stimulation there was actually a drop in global protein synthesis accompanied by an increase in activity of a protein called eEF2 kinase, and an increase in CaMKII synthesis. The activation of eEF2 kinase slows down the elongation phase of translation. The idea here is that mRNAs that are good at initiating translation may actually be at a disadvantage during this state because they get stuck further down the road. This would shift the balance to mRNAs that have a hard time with initiation, potentially like CaMKII. One cause of initiation difficulty may be complicated secondary structures near the beginning of the transcript that make it hard for ribosomes to scan down to the start codon (the codon that signals the first amino acid in the newly forming protein).

Speaking of start codons, one further example where global protein synthesis inhibition can actually be good for specific translation is that of the GCN4 upstream open reading frames. This mechanism hasn't been shown to play a role in plasticity-related protein synthesis yet. Most of the details have been worked out in yeast. In response, to amino acid starvation, an enzyme called GCN2 is activated. It in turn phosphorylates (sticks a electronegative, function-altering phosphate group on) a protein called eIF2alpha. When eIF2alpha is phosphorylated it serves to inhibit production of a key component in translation initiation (called the ternary complex). So it is harder to initiate translation. The ternary complex carries the first amino acid of every protein, methionine, which matches up to the start codon, AUG. The mRNA for GCN4 has several AUGs that are not the start codon for the actual protein. These AUGs are associated with upstream open reading frames (uORFs), sections of mRNA sequence that code for little chunks of protein that don't do any good. These are like 8 or 9 amino acid peptides we're making here. When amino acids are around and all is well with the cell, ribosomes start at the cap of GCN4, find uORF1, translate it, find another uORF downstream, translate that, and fall off. They don't make it to the actual protein-coding part of the transcript. When initiation is inhibited, they can't get a new ternary complex in time to translate the later uORFs. They finally get a new ternary complex in time to read the actual open reading frame of the GCN4 gene. So once again, global protein synthesis is turned down, but an mRNA with a funky 5' end gets the advantage.

I find it interesting to consider that dendritic protein synthesis following synaptic activity might actually contain two components. In the first couple minutes after stimulation, global synthesis might be downregulated and certain RNAs with special attributes that normally weaken their translation are upregulated. In the minutes to hours afterward, global synthesis is upregulated and more general synapse building proteins are manufactured. The synthesis could come in waves coordinated by complex secondary structure and ribosome-obstructing elements in the 5' untranslated regions of certain key mRNAs. Strangely, the intriguing Scheetz et al. finding released back in 2000 has not been followed up. One wonders if others have tried and been unsuccesful or what.

10 Questions for Bruce Lahn   posted by JP @ 10/10/2006 04:50:00 PM

Bruce Lahn is a Professor of Human Genetics at the University of Chicago as well an Investigator at the Howard Hughes Medical Institute. In 2004, he was on the "Top 40 Under 40" list by Crain's Chicago Business. Specifics of his research can be found on his faculty page. Our 10 questions are in bold below the fold.

1. One of the major trends in hominid evolution has been increasing brain size, with the somewhat confusing caveat that modern humans break that trend, with smaller brains than both Neanderthals and some earlier hominids. Many hypotheses have been proposed to explain this, from sexual selection for intelligence to selection pressures from culture. Do you have a favorite hypothesis? What evidence do you think could settle this issue?

Brain size is just a proxy for cognitive abilities. This proxy is very robust over long evolutionary periods (millions of years). But on a short time scale, fluctuation in brain size may not correlate well with cognitive abilities. Within humans, for example, brain size is only weakly correlated with cognitive test scores such as IQ (only about 15% of the variation in IQ can be explained by difference in brain size). Given this, perhaps we should not make too much out of the cognitive significance of brain size changes on a short time scale.

2. Your work on genes involved in human brain evolution (i.e. ASPM and microcephalin) has focused on amino acid changes. It has been hypothesized that most of the differences between humans and chimps are due to regulatory changes. Do you feel this is still a viable hypothesis? Do you consider your work a challenge to this hypothesis?

The hypothesis that most human-chimp differences are due to regulatory changes is proposed in the absence of any data. So, I don't place too much weight on this hypothesis to begin with. Nevertheless, I acknowledge that this hypothesis has influenced the thinking of many people. Our work showed that coding region evolution is likely to be important for human brain evolution. In this regard, it can be considered to be a challenge to the hypothesis. However, our work by no means argues that regulatory changes are necessarily less important than coding changes. So, the jury is still out.

3. The aforementioned work on microcephalin and ASPM touched some nerves, due mostly to two issues: the difference in frequency of the derived haplotype in different populations, and co-incidence of major moments in human cultural evolution with the appearance of these derived haplotypes. Do you regret anything you wrote in either of those papers?

On the one hand, I don't regret the things we wrote in the papers because they were scientifically justified and the speculative nature of some of our statements was clearly indicated as such. On the other hand, I can appreciate why some people might be concerned over the possibility that our results could be over-interpreted or even mis-interpreted to advance certain ideas about race and ethnicity, especially by people with certain political agenda. Our society, given its sordid history on race-related issues, is very confused about how to deal with racially and ethnically sensitive topics. As a result, science and politics get mixed up when they relate to these topics. I personally feel, like many other scientists, that science should be separate from politics. In particular, science should meet the same burden of proof regardless of what political implications it might have. But this may be too idealistic if not naive. I feel I am still learning how to handle such issues in a way that is honest to the science while at the same time sensitive and respectful to political and cultural needs.

4. You've speculated that humans will, at some time in the future, speciate. The evidence for clinal speciation in other taxa certainly supports this possibility. One possible counterargument is that germ-line genetic engineering or even pre-implantation genetic screening could lead to the human population becoming more homogenized, preventing the evolution of barriers to gene flow. What role do you see for technology in the future of human evolution?

I think we as a species now stand at a watershed moment in the history of life. For billions of years, evolution of life forms has been governed by the Darwinian process of random mutations followed by selection. Now, we are about to revise that principle dramatically by genetic engineering. Instead of starting with random mutations, of which only very few are advantageous, we can now prospectively change our genome (and the genomes of other species) in ways we intend. In a sense, genetic engineering will make Lamarckian evolution a reality. Given the revolutionary nature of this new technology, it is impossible to predict where the technology will take us into the future. But suffice it to say that genetic engineering, coupled with other technologies such as pre-implantation genetic screening, would likely speed up evolution enormously, and create life forms, including those derived from our own species, in ways that the Darwinian process can never hope to accomplish.

5. You've published a paper noting a correlation between mutation rate and the ratio of nonsynonymous to synonymous mutations in a gene. This ratio forms the basis for many tests for selection. What's the best way to interpret such a test? You do much molecular work-- how can one decide, using both statistical and molecular evidence, that the story for selection on a locus has been decided one way or another?

It is still debated among experts as to how to interpret the ratio of nonsynonymous to synonymous substitutions. The major difficult arises from the fact that both positive selection and relaxed constraint produce a high ratio. When a gene has a low ratio, one can argue that it has evolved predominantly under purifying selection. But when a gene has a high ratio, it is not clear whether it is due to strong positive selection, or relaxed constraint, or a bit of both. So, unless the ratio is very much greater than 1, it is not possible to conclude what a high ratio means. This is where other statistical and molecular evidence is needed. There are no clear-cut rules on what evidence can be considered "enough" for establishing (or refuting) positive selection. But the best cases usually involve multiple lines of evidence coming from several independent perspectives that are consistent with each other.

6. A lot of researchers studying human population genetics and evolution are strictly data miners (i.e., they generate/publish no original data). There are limitations to such an approach, as it depends on the available data and prevents certain analyses from being performed. Do you expect to see more research groups turning into pure data mining labs in the future? Or will there still be a place for independent labs generating their own data (for example, resequencing a gene in multiple individuals to study the polymorphism)?

Given the explosion of genomic data in the last decade or so, which shows no sign of slowing down any time soon, there is likely to be a proliferation of pure data miners just because there is a niche for them. But I suspect that many interesting findings will still require the combination of data mining and wet experiments to provide key pieces of data not already available in public databases. In this regard, labs that can do both data mining and wet experiments can have an advantage over labs that can only do data mining.

7. The politics behind the funding of stem-cell research in the US have sometimes obscures the actual science. As someone who works in the field, where is it headed? What is truly feasible in terms of medical progress using an approach based in stem cell research?

I personally feel that the promises of stem cells as a direct reagent in the treatment of disease are grossly exaggerated. I think it will be a very long time before Parkinson's disease or Alzheimer's disease could be treated by introducing stem cells (or their derivative cells) into a patient. However, stem cells offer a model for studying developmental processes. As such, stem cell biology will ultimately make valuable contributions to our ability to better understand disease and develop treatments. So, I believe that the future of stem cell research lies in its potential as a research tool, and to a lesser extent, its ability to provide direct cure for disease.

8. Much of your work on stem cells is done in collaboration with a center in China. What is the attitude towards such research there, and how does it compare with the attitude here in the US?

The attitude is much more progressive relative to the US. Religion is not a dominant force in molding Chinese cultural traditions, and people are generally not married to a particular doctrine. This attitude provides greater flexibility for stem cell research.

9. Ian Buruma has noted that many Chinese dissidents have converted to Christianity, while David Aikman, in "Jesus in Beijing", argues that the Christianization of much of China will alter geopolitics. How accurate do you think is the perception by many Westerners that Christianity is filling the ideological void left by the fall of Marxism-Leninism?

I tend to agree that Christianity is filling an ideological void left by the dying out of the old communist ideology. But whether China will be Christianized is a separate matter. There is plenty of Chinese who are strongly opposed to the idea of allowing religion to play a major role in the culture. I suspect it will be a major uphill battle for one religion, be it Christianity or otherwise, to spread beyond a few limited sectors of society. But this is just my guess.

10. Looking back, would you make any changes in your educational path? If so, what?

Looking back, I might have chosen economics instead of biology, as it might have allowed my work to have a broader impact. But it's a tossup, and my feeling may well have stemmed from my constant impatience with lack of progress in my own work and therefore the perception that grass is greener on the other guy's pasture


Putnam: Diversity is weakness   posted by dobeln @ 10/10/2006 01:36:00 AM

It appears that Robert "Bowler" Putnam is ready to publish his book on the effects of diversity:

From the Financial Times:

A bleak picture of the corrosive effects of ethnic diversity has been revealed in research by Harvard University's Robert Putnam, one of the world's most influential political scientists.

His research shows that the more diverse a community is, the less likely its inhabitants are to trust anyone - from their next-door neighbour to the mayor.

The core message of the research was that, "in the presence of diversity, we hunker down", he said. "We act like turtles. The effect of diversity is worse than had been imagined. And it's not just that we don't trust people who are not like us. In diverse communities, we don't trust people who do look like us."

Needless to say, Putnam serves up this rather hard-to-digest message with a large helping of "the usual":

Prof Putnam stressed, however, that immigration materially benefited both the "importing" and "exporting" societies, and that trends "have been socially constructed, and can be socially reconstructed".

In an oblique criticism of Jack Straw, leader of the House of Commons, who revealed last week he prefers Muslim women not to wear a full veil, Prof Putnam said: "What we shouldn't do is to say that they [immigrants] should be more like us. We should construct a new us."

A bit uninspired. Will it be enough to save his spot on the circuit? Time will tell.

Monday, October 09, 2006

Nature Genetics Podcast   posted by Coffee Mug @ 10/09/2006 10:43:00 PM

Nature made a genetics podcast. I can't tell if this is a special feature just for the ASHG meeting or if it will continue.

Dendritic translation and memory   posted by Coffee Mug @ 10/09/2006 08:15:00 PM

The recent Science paper by Raab-Graham et al. that rosko linked shows dendritic synthesis of a protein modulated by various pharmacological agents. A review by Sutton and Schuman came out in Cell on the same day and serves as a good guide to the importance of dendritic protein synthesis in synaptic plasticity and memory. Raab-Graham et al. speaks to one of the issues in the S&S review, namely, how to identify proteins that are actually being synthesized in dendrites. What follows is the Readers' Digest guide to key issues identified by S&S and an interjection showing where the Science paper fits in.

Why are we concerned with local/dendritic protein synthesis? Well, first, why are we concerned with protein synthesis at all? Memories appear to require protein synthesis for permanent storage. People have studied this in numerous learning paradigms by injecting protein synthesis inhibitors into slugs or rodents at different times after training sessions. Without going into specifics and caveats, you can generally take it that these inhibitors are only effective in disrupting the memory if they are administered within the first couple or three hours after training. The same goes for cellular models of learning and memory (i.e. long-term potentiation, LTP). So in order to stabilize a nascent memory new proteins must be synthesized.

The end result of all of this protein synthesis must be the modification of synapses. We know that not all of the synapses on a neuron are potentiated in response to stimulation, so we need the new proteins to act only at certain synapses, presumably synapses that are in some way related to the ones that drove the protein synthesis. The proteins could either be generated in the soma and trafficked to the proper portions of the dendrite or they could be synthesized from preexisting mRNAs in the dendrites. You can see some advantages to the latter proposal as all of the action can happen in one little area without expending energy to carry around all those proteins and figure out a zipcode system to make sure they end up at the right inputs. In ways it is similar to the contrast between using snailmail to ask for a reprint and receiving the pdf via email so you can print it off yourself next to your desk.

Not to mention, as S&S lay it out, polyribosomes (protein printers) were shown in dendrites by Steward and Levy using electron microscopy. It remains possible that they are there performing a housekeeping role and that plasticity-related synthesis is carried out in the soma. We do know that dendritic synthesis can do the job of maintaining LTP into the protein synthesis-dependent phase. Some of the best demonstrations involve microsurgical dissection where the dendrites are physically separated from the cell body prior to LTP induction. Others have shown that restricting protein synthesis inhibition to the dendrites still blocks late-phase LTP.

It has been more difficult to show the necessity of dendritic protein synthesis in live, behaving animals. The closest anyone has come was a transgenic mouse carrying a mutated version of the alpha subunit of calcium/calmodulin-dependent protein kinase II (CaMKII), one of the leading candidates for the plasticity-induced, synapse-altering protein. The mouse lacked a chunk of the CaMKII mRNA that doesn't code for protein, but instead carries a dendritic localization signal. So there can be no local synthesis of this really important synaptic protein because the mRNA isn't there locally to synthesize. These mouse had impaired memory. But alas, this mouse and all the other mice that have been used to study protein synthesis and memory are second-generation transgenics, meaning that the genetic manipulation is not tightly restricted in the temporal domain. Compensation is the rule not the exception, so if we screwed up the system, I expect lots of things besides CaMKII mRNA localization were altered in this mouse. In memory research, timing is everything. Not only could the mouse be just globally weird, but the manipulation could be affecting the acquisition, storage, maintenance, or retrieval of the memory.

S&S suggest a number of areas where basic knowledge related to the issue of local protein synthesis is lacking.

1) What mRNAs are in dendrites? Should we be identifying each one individually or will microarrays using samples that ostensibly carry only dendritic or synaptic mRNAs do the trick? It's a classic quantity vs. quality issue in my mind. It would be nice if you could do a neuronal cell line array like people have been doing with yeast arrays . I can imagine a library of mammalian cells (either a neuronal line or a stem cell-line treated with neuronal differentiation cues) containing MSH2 tags in each mRNA and an MSH2-binding protein-GFP hybrid. Sorry, I'm indulging myself. There is probably a more efficient solution than what immediately pops into my head.

2) Which proteins are actually synthesized in dendrites? This is the part that Raab-Graham et al is getting at. It is not good enough to show which proteins can be found in dendrites, you have to show that they appear there in response to synaptic activity. The CaMKII mouse mentioned above provides one way to examine the issue. Restricting the mRNA to the soma led to a large decrease in synaptic CaMKII. This is reasonable evidence that synaptic CaMKII comes from dendritic CaMKII mRNA. Also, the amount of CaMKII in dendrites far from the cell body jumps up following stimulation, so fast that it can't have been transported from the soma. This protein, and now Kv1.1, are the only ones that have undergone this type of analysis. The CaMKII studies didn't require any photoconvertible protein hybrid though, so I'm a little uncertain as to why Raab-Graham et al had to go through all that technical trouble. Also, if my understanding is correct, they could have reached the same conclusions using FRAP (fluorescence recovery after photobleaching). Rather than looking for a new green signal after converting everything to red, they could have simply looked for a new green signal after bleaching out all existing fluorescence. Paging Dan Dright.

3) How specific is LTP? While many use the terminology, S&S note that we haven't shown that LTP is synapse-specific. When ribosomes are found in the dendrites they are found near synapses, at the bases of dendritic spines, not in synapses. Synaptic tagging experiments have shown that proteins synthesized due to strong stimulation at one input can be 'captured' by other synapses receiving weak stimulation. So the locally synthesized proteins aren't all that faithful to the inputs that led to their creation. Some have used two-photon glutamate uncaging to try to stimulate individual synapses, but still it is not clear that the changes are restricted to just those receiving stimulation. Perhaps multiple nearby synapses are affected at once. There is some evidence that synapses near to each other might at lease share input modality, so you could potentially still be encoding a specific association between stimuli using clustered plasticity.

4) One last issue, and I'll keep it short. Protein synthesis inhibitors usually only have effects in the first few hours after training at best, while memory persists for weeks, months, or years. Proteins turn over though. We really just don't know how fast most synaptic proteins are degraded. They could last long enough to do the job of maintaining memory. If not, perhaps the memory can be maintained for the amount of time it takes for the inhibitors to wear off. You can't really address this question by extended protein synthesis inhibition because you will eventually end up harming the cells irreversibly. So we need to measure some protein half-lives.

A few of these questions seem like they would be trivial for people outside of the neuroscience community, people who have expertise in high-throughput biology. It's not clear to me why their wild ever-shifting attention hasn't landed on synaptic plasticity yet, but if any of you are reading this maybe you could just get some physiologist to hand you tissue (preferably synapse-enriched) on a time course after LTP. Run a microarray. Do some mass spec proteomics. Tell us which proteins there are more or less of before and after. That's not that big a deal right? I'm pretty sure I can find you the tissue if you are having a hard time.

Global phenotypic variation in personality traits   posted by agnostic @ 10/09/2006 12:00:00 AM

Part 1 of my crash-course on personality went over the psychometric and neurophysiological basics (to the extent these are currently understood). Part 3 will look more at the search for candidate genes that influence personality traits, as well as their importance in recent human evolution. This Part will be brief, focusing just on global variation in personality phenotypes. So far there are three largish datasets on the mean level of various personality traits across cultures: Lynn & Martin (1995), which synthesized a host of studies that used the Eysenck Personality Questionnaire; and Allik & McCrae (2004) and McCrae, Terracciano, et al. (2005), which used the Big Five's NEO-PI questionnaire. I'm going to focus on the first collection of data since they were collected from a variety of individuals within a given culture and have large Ns (roughly in the upper hundreds or over 1000 for each country), whereas the latter two were restricted to college students and for some cultures have smaller Ns (roughly in the lower-to-mid-hundreds). Here is a graph plotting different countries by their mean level of Extraversion and Neuroticism (units aren't important, basically how many questions you answer in favor of E or N), with the yellow axes representing the unweighted global medians:

[See Note 1 for explanation of why Israel is red.] I tried to make it as legible as possible, and the abbreviations are clear (so "Rom" means Romanian, not the Roma). The accompanying graphic that I dug up online shows the Four Temperaments, which are essentially what the four quadrants of an E x N coordinate plane represent, along with some related characteristics. The list of natural language words that describe personality traits can be factor-analyzed, and this approach yields the same Big Five traits from the NEO-PI (Saucier & Goldberg 2001). A word like "excitable" would load positively on both the E and N factors, for instance. Note also that "anxious" reflects both low E and high N -- most interesting personality phenotypes will be composites like this. However, remember that the EPQ and NEO-PI measure continuously varying traits (the score conveys both direction and magnitude), unlike the typological approach of the Four Temperaments and the psychiatric manual DSM-IV.

Other characteristics don't relate much to E or N -- "dependable" or "orderly" are more related to the Big Five factor Conscientiousness. Recall that the EPQ measures a trait called Psychoticism, which is like the interaction between Big Five Agreeableness and Conscientiouness, but inversely related to them -- that is, someone who scores high on Psychoticism would score low on A and C. This multiplicative interaction will skew the distribution much more so than if just A or C or an additive interaction were chosen, and sure enough, in the chart below, notice that the scores on Psychoticism are much lower across countries than on E or N -- the highest score is 9.1, which is barely at the minimum score on either E or N, indicating that the bulk of the Psychoticism distribution is packed into the low end. And unfortunately, you can't decompose a product into a unique pair of multiplicands, so if one person's (or country's) Psychoticism score is higher than another's, that could be because of higher A and equal C, vice versa, or higher scores on both. Having said that, here is the list of Psychoticism scores, in descending order, from the studies synthesized by Lynn & Martin:

Czechoslovakia 9.1
India 8.1
Yugoslavia 7.4
Hong Kong 7
Australia 6.9
China 6.7
Germany 6.1
Uganda 6
France 5.5
Greece 5.4
Iran 5
Lithuania 5
Japan 4.8
Finland 4.7
Mexico 4.5
Egypt 4.4
Italy 4.4
Puerto Rico 4.4
Singapore 4.3
Bangladesh 4.2
Canada 4.2
Sri Lanka 4.2
Bulgaria 4.1
Brazil 4
Korea 4
Hungary 3.8
United Kingdom 3.8
Nigeria 3.6
Russia 3.6
Iceland 3.5
Israel 3.5
Romania 3.5
United States 3.3
Spain 3
Netherlands 2.8
Portugal 2.6
Norway 2.2

Now, Hong Kong would not be a financial giant if the average citizen scored very low on Conscientiousness; that is, if they were not driven to achieve, had little sense of order / structure, were not reliable / dependable, etc. So their high score here likely reflects having very low Agreeableness: distrust of others, more antagonistic, less empathy, etc. -- more competitive, in other words. I know nothing about Czech people, so I have no idea whether their scoring highest is due to very low A but average C, very low C but average A, or very low on both. Those who are thinking of the influence of having lived under Communism -- good guess, but political systems don't seem to shape personality (at least, not that quickly...). When the Berlin Wall fell, East Germans and West Germans were virtually indistinguishable by personality trait measures, though their political and social attitudes differed (see Note 2). So again, try not to read too much into the above list as far as A and C go, unless you know the population well enough to tell that their score reflects A more than C, or whatever.

There are two other large surveys of national levels of personality traits, but as mentioned, the Ns for each country are lower, and they mostly reflect on college students. Now, restriction of range effects for personality won't be as awful as with intelligence, but still, college students may not be entirely representative of their populations. I imagine this would be especially apparent in cultures where college students do nothing but extensive rote memorization, don't have time for social lives, and are expected to accept their teachers' views rather than question and challenge them. Presumably, generalizing from such a sample would make the population appear more introverted than it truly is (as in Nigeria or India, for example). With this warning in place, here are the visuals from each Big Five study:

Some differences in the format compared to before: the scores are T-scores, and the plots are the result of multidimensional scaling, which tries to crunch the variation across the separate Big Five traits into variation among fewer dimensions. In both graphs, the vertical axis is maximally aligned with N and the horizontal with E, though they are not strictly E and N as before since other traits have been crunched in. In the first graph, a positive value on the horizontal also represents higher O and lower A, while a positive value on the vertical also represents lower C and lower A. In the second graph, a high value on the vertical also represents lower C and lower A, but now a high value on the horizontal also represents higher A (unlike before), though it still also represents higher O. Again, though mostly intact, this flip-flopping is likely due to smaller and less representative samples than in the Eysenckian studies discussed at the beginning.

There's clearly much more to say, but I'll leave it at that for now. The next Part will try to tie the first two Parts together by looking at genes and evolution.

Note 1: I don't question Israel's high score on E, but it's low score on N would make it the most emotionally stable population on the planet by a longshot. While there may be some differences between American and Israeli Jews (most of whom are Ashkenazim in both countries), there is no way the data point can be accurate. It is likely a typo (this is a Lynn article, after all, so a typo wouldn't be unusual). In reality, their N score is probably above the global median, though by how much, who knows? I left the point as stated in Lynn's article, but it is likely somewhere above the data point for India, in the upper-right quadrant.

Note 2: Quoth Hofstede & McCrae (2004):

Angleitner and Ostendorf (2000) provided some provocative evidence [...]. They compared mean levels of NEO-PI-R scores from former East and West Germans. Despite decades of enforced communism in East Germany that included control of law, education, and mass communications, the only difference between the two samples was that West Germans were slightly higher in openness than East Germans.

The ref is: Angleitner & Ostendorf (2000, July). The FFM: A comparison of German-speaking countries (Austria, Former East and West Germany, and Switzerland). Paper presented at the 27th International Congress of Psychology, Stockholm, Sweden.

Sunday, October 08, 2006

The hotspot paradox   posted by JP @ 10/08/2006 09:55:00 PM

In the comments of a previous post, rikurzhen asks the following question:
do we know enough about recombination hot spots to say if they are heritable? if so, could the location of a hot spot itself be under selection?

I responded that it would be tough to tell whether or not hotspots are heritable or not, but this isn't entirely true-- I limited myself to thinking about humans. On a bit of further reading, I can now definitively say yes, certain DNA sequences are more likely than others to initiate recombination, and these sequences are (obviously) heritable.

The interesting thing is that the very existence of hotspots implies a paradox. I highly recommend the introduction to this article for those looking to understand why this is so. Here's a good summary of the problem:
Sexual recombination is one of the main forces shaping eukaryote evolution, but implicit in its mechanism is a serious paradox. The mechanism, called double-strand break repair, was first proposed for fungi in 1983. It has become increasingly well understood and well supported in a wide variety of organisms, and double-strand DNA breaks (DSBs) are now thought to be the primary initiators of meiotic recombination in eukaryotes. DSBs usually occur at chromosomal sites called recombination hotspots, whose evolutionary persistence is at the heart of the paradox. DSBs appear to frequently cause destruction of the DNA sequence specifying the hotspot and replacement of this sequence by the sequence of its homolog. Over many generations this self-destructive mechanism is expected to cause all active hotspot alleles to be replaced by alleles incapable of initiating DSBs. The paradox is that this has not happened.

However, the story may be more complicated, at least in humans. From here:
Haplotype analysis around both hotspots identified active and suppressed men sharing identical haplotypes, establishing that these major variations in the presence/absence of a hotspot and in quantitative activity are not caused by local DNA sequence variation

It seems likely, to me, that there must be some mechanism that maintains a certain number of recombination events on a chromosome (recall from your molecular biology class that at least one crossing-over must occur on each chromosome in meiosis I to guarantee proper segregation of the chromosomes). The actual location of the crossing-over may be determined by a number of factors, local sequence variation included. Perhaps this recombination-guaranteeing system, which itself is not part of the crossing-over, could resolve the paradox.

Possibly of Interest   posted by John Emerson @ 10/08/2006 12:26:00 PM

I have published several pieces on my other site recently which some people here might be interested in.

The multiculturalism piece would probably fit here, but it was already cross-posted at The Valve. The refutation of the existence of God (which got a link on Ophelia Butler's secularist Butterflies and Wheels site) is probably a little too jokey for GNXP. The piece on Amartya Sen is perhaps of interest to those who were interested in my earlier piece here on ev-psych and econ. (Bonus: a piece on Tyler Cowen and economic rationality).

What is "culture" in multi-culturalism?

I doubt, therefore God does not exist.

Amartya Sen: Rationality and Freedom.

Add: Tyler Cowen on Economic Rationality

Why Lakoff matters   posted by Razib @ 10/08/2006 10:12:00 AM

Here is a snip from Chris' updated conclusion from his post smacking Lakoff every which way:
When I first started writing this post, I used the title The Devil v. The Devil, but that seemed a bit too silly. It was meant to indicate my distaste for both Lakoff and Pinker...I point this out to make it clear that my only real stake in the debate between two people I sincerely dislike (at least professionally; I don't really know either of them personally, though I've met them both) is the science, and in this case, Pinker is right on the science, and Lakoff is wrong. Furthermore, instead of presenting intellectual arguments to convince us that he's right, Lakoff just makes shit up.

Here is a comment from my other weblog:
You also ignore what is the vast majority of the post: countering Pinker's mischaracterizations. Lakoff takes the time to do extensive citing of his positions. I know that 's not convenient for a lot of good "shocking" and "thrashing," but it does make a convincing argument. Not that it matters anymore.

I don't know much cognitive science, so I wasn't familiar with a lot of the terminology and literature that Lakoff tossed out in the second half of his argument, so of course I wouldn't address that part of the essay! Now, I did strongly suspect that Lakoff was trying to bullshit us though. I am not totally ignorant of cognitive science, and I didn't think Lakoff's characterization of the "new" vs. "old" model was correct, and I also was skeptical of his citation of Kahneman and Tversky as supporting his ideas as I am familiar with their project. Chris laid out in explicit detail the shit that Lakoff was pulling, and basically confirmed my sense that he was trying to "dazzle" us with terminology (for whatever you think of Pinker, his essay was at least an attempt to communicate in plain English!).

I wanted to highlight the comment above because it elicited in me a sense of deja vu. Where else have we heard the "you haven't refuted all the citations!" or "you haven't addressed all the arguments!" canard? This is the sort of thing that crops up in the Creationism/I.D. debates all the time, "you haven't refuted all of Dembski's arguments based on information theory!" Or, "well, the second law of thermodynamics refutes evolution!" Or, "well, evolutionary biology is a mover philosophy, not a science." And so on. Now, I know a little about evolution, so if someone tries to show how Fisher's Fundamental Theorem of Natural Selection refutes the long term possibility of evolution because of the exhaustion of genetic variation due to selection, I can respond in a quick & compact manner. It isn't hard to respond to the thermodynamics talking point, and Creationists don't even know what they're saying so it isn't a big deal when you point out to them a close vs. open system distinction (quite often they expect you to be dumbfounded and they've won the point since you couldn't respond, but they have lots of other gibberish so they aren't totally dejected with that miss).

I am not hinting at an analogy between Lakoff's form of cognitive linguistics and Creationism to simply attack Lakoff because I feel he is condescending to the Right. I never really cared much about framing until I read Chris' weblog and understood that Lakoff wasn't as revolutionary or mainstream as he presented himself as (I had gotten hints of this before). Cognitive science is a new field, and there aren't as many established models and paradigms, so in terms of the magnitude it is out of line to call Lakoff's ideas in relation to mainstream cognitive science similar to the relationship of Creationism to evolutionary biology. But, the vector points in a similar direction insofar as Lakoff's ideas are out of the mainstream, and, he attempts to present his own viewpoint as accepted orthodoxy, or the "new wave" which is marginalizing the older models. From all I can gather this is false, Lakoff works out of the mainstream, so no matter the quality of the science he is fundamentally mischaracterizing the nature of the scientific debate by framing (for lack of a better term) other cognitive scientists as the dead past (and his characterization of the ideas that emerged out of the cognitive revolution as being traced to Descartes is a bit idiosyncratic, though I think I can understand what he's trying to say and where he's getting this from, I think it is giving the audience a fallacious impression, the primary aim of which reinforce the perception that Lakoff = new, other guys = old). This is very similar to Creationists who argue that evolution is the past and that Dembski and Michael Behe are the theorists and researchers who we have to focus on for the future. No matter the nature of Dembski or Behe's work, the idea that they are the researchers who are revolutionary and the wave of the future is a total falsehood. I specifically demand anyone who promotes Intelligent Design to concede this point, or I won't talk to them, because there's not point in having a debate where one of the parties commits themselves to a false perception of the nature of scientific culture as it is. Paradigm shifts do happen, but until they do we must give appropriate respect to the orthodoxies of the day. Science is a system which depends upon acknowledging the accumulated body of knowledge of the present to build bridges into the future. You can reject biology as it is now, but, I do not accept individuals attempting to recast the state of the debate in biology by inventing pure fictions. This is also a point I bring to the fore in other debates; e.g., as to whether the Indo-European languages are indigenous or exogenous to the Indian subcontinent, when I have engaged brown nationalists who enjoy entertaining fantasies on par with Creationists I grant them the right to indulge their fantasies, but I reject their attempt to assert that the state of the consensus in philology is in flux or different from what it is. In other words, I give them the right to reject philology as a scholarly field, but I don't allow them to simply reinvent what it is. Similarly, I am not worried if Lakoff and his acolytes reject all of cognitive science, but, I will not accept them attempting to characterize the state of the consensus as something it is not. That is poison for the scientific spirit, and it isn't as if there isn't enough bias, politics and error in science already.

Moving specifically to Lakoff's ideas and their relation to the liberal/progressive camp, as Chris points out it is precisely liberals who have the most to lose from espousing his ideas as if they have scientific validity. I think that is also Pinker's central point. Science can not become engineering if it is not valid science, and Lakoff's ideas are precisely attempting that translation, turning scientific models into social engineering. Young Earth Creationists have a "water canopy" hypothesis, but attempts to model it unfortunately always run into the problem that it predicts runaway greenhouse and turns the planet into Venus in short order (water vapor is a potent greenhouse gas). Similarly, attempts to use Lakoff's models to shape the public discourse are likely to have disasterous consequences if the science is shaky in the first place. Fundamentally I think the appropriate analogy to liberals using Lakoff's ideas about cognitive linguistics is when conservative Protestants justify their public policy prescriptions via the Bible (e.g., a "Biblically base society"), or when conservative Catholics appeal to Natural Law reasoning. Though the Bible and Natural Law are convincing within your own camp, trotting out these arguments to those who don't share your presuppositions is likely to induce laughter and hilarity (e.g., as when congressmen mocked Clarence Thomas for entertaining Natural Law). In conservative Christian circles "because the Bible says so!" is a very powerful talking point, but once you move outside them using this is likely to weaken your position and render you less credible. Rather, one must find a common ground, primarily via a sort of utilitarian argument. Through these debates one can flesh out differences in values and perceptions of what the "Good Society" is, but the argument still serves that purpose even if it doesn't resolve the disagreemants. Liberals and conservatives can argue whether the median, variance or skewness of income important, but through argument they can get a better model of how the "other side" conceives of the world.

In short, I think the problem with Lakoff's ideas are two fold: 1) the science is probably wrong, so it has little utilitarian value aside from enriching Lakoff 2) the false perception that the science is correct and can be used to persuade people basically leaves liberals totally vulnerable to being laughed at (a lot of the stuff that Lakoff acolytes say about the Right is giggle-inducing! Pinker is describing a real phenomenon, as I've chuckled myself). If I was a particularly partisan non-liberal I would probably let it rest, as it is good for the Right for the Left to hold to Lakoff closely, just as it is good for the Left for Christian fundamentalists to continue speaking like raving Bible-thumpers outside of their own circles. But in the end politics is epiphenomenal, the truth shall outlive us all, and only one culture has spawned science in the history of our species. That demands our reverence (at least mine) far more than who will win in 2006, or 2026.

Saturday, October 07, 2006

Common variant for anxiety   posted by JP @ 10/07/2006 05:33:00 PM

Studies that look for an association between a genetic variant and a trait are often inconsistent, finding an association in some studies or some populations, but not others. This could be for a number of reasons-- small samples sizes, heterogeneity, or difficulty quantifying the trait, among other things. Or it could simply be that there's no association to find.

However, it's certainly strong evidence for an association if inducing the variant allele in a mouse also induces the trait you're looking at. This paper does an excellent job of that, pretty much conclusively settling the issue of whether a variant in a certain brain-expressed gene is invloved in anxiety. Mice without the variant are normal, mice with the variant display more anxious behavior (avoiding the middle of an open area, for example). Simple as that.

The causal allele is present at a frequency of 20-30% in Caucasian populations, so it is perhaps a large contributor to normal human variation in anxiety. And it's also perhaps a prelude to finding common alleles that explain some of the variation of other cognitive phenotypes.

Male sex workers in Pakistan   posted by Razib @ 10/07/2006 02:30:00 PM

Marginalised male sex workers vulnerable to HIV/AIDS:
While such behaviour is strictly illegal, homosexuality is fairly widespread in Pakistan. Under the country's Islamic laws, sodomy carries a penalty of whipping, imprisonment or even death - but the fact on the ground is that it is also for the large part silently accepted.

I am not too concerned with the HIV/AIDS angle as I suspect nearly universal male circumcision will dampen the proportions even if the rate of growth is high in the short term (if 0.1% is correct there is no where to go but up!). Rather, I always find this stuff about homosexuality in the Muslim world interesting, because Muslims are so rhetorically medieval on a little-bit-of-gay. One thing is that lying and "keeping up appearences" is such a big deal in most cultures. I like the relative candor of the Anglo-Saxon world (I don't have personal experience of stuff besides Islam/South Asia and the Anglo-Saxon world). My mother makes many comments to the effect of "in Bangladesh we don't have that." Aside from the fact that she hasn't lived there for a generation, she is also a rather sheltered person who was raised in privileged and pampered circumstances. Reading the paper in Dhaka 2 years ago (English language) there were reports of the prostitutes in Dhaka's red-light district trying to unionize, and the neighbors complaining about its expansion. Also, there were concerns about a major downtown porn stall which wasn't being shut down because the cops were getting bribes in the form of porn.

(via Pass the Roti)

Dogs might not be descended from wolves   posted by Razib @ 10/07/2006 02:14:00 PM

RPM has the skinny. Like humans, dogs are interesting, way more than Drosophila or C. elegans.

Pinker vs. Lakoff   posted by Razib @ 10/07/2006 01:51:00 PM

Update: Yo slutz, listen up here, a pro is in the house. Chris of Mixing Memory starts:
I don't really know where to start on this. Lakoff's reply is one of the most intellectually dishonest pieces of writing I've seen from a cognitive scientist, and if anyone other than Lakoff had written it, I'd probably just ignore it. But Lakoff is not only famous, he's influential, and more than a few liberal bloggers take him seriously. So I feel compelled to say something. I guess the best way to go about this is to detail their disagreements, and show where Lakoff sinks to all new lows in defense of his position.

Read the whole thing & call 911, someone's been smacked down!
End Update

A week ago I posted about Steven Pinker's recent TNR essay slamming George Lakoff. Lakoff now has a rebuttal up. In the interests of comparison both the essays are below, next to each other.

A few points:

1) I'm not a "progressive." No matter the reality of the science when I've read Lakoff's work (e.g., Moral Politics) I get the sense his goal is to tell liberals how non-liberals think, and why they think it, and implicitly, where their thinking goes wrong. There's a patronizing and condescending tone to it which is off putting. But fine, science isn't always there to confirm one's own self perception. Pinker is spot on when he says:
The problem with this burlesque is not that its targets don't deserve criticism. It's that it will backfire with all of its potential audiences. Any of his Lakoff's allies on the left who think that their opponents are such imbeciles will have their clocks cleaned in their first debate with a Young Republican. The book will be red meat for his foes on the right, who can hold up his distortions as proof of liberals' insularity and incomprehension. And the people in the center that he really wants to reach will be turned off by his relentless self-congratulation, his unconcealed condescension, and his shameless caricaturing of beliefs with which they might have a modicum of sympathy.

As a right-winger I have enjoyed many a conversation where I've shocked and thrashed innocent liberals who have never talked to a real conservative. I'm not much of a conservative, but I don't bow to the same Gods as most liberals so my opinions can be quite blasphemous and disconcerting. Lakoff's work doesn't seem to help. What's the point of science if you can't predict?

2) In Lakoff's response there is a lot specific detail about cognitive science literature which I find hard to follow. But, my impression is Lakoff is really overselling the impact of his brand of cognitive linguistics. Also, I am 100% sure that Pinker has little issue with many of the thinkers cited in the beginning of Lakoff's essay to rebbut Pinker's conception of "how the mind works" (e.g., Kahneman and Tversky). In other words, I think Lakoff is caricaturing to a great extent what he terms the "old model" in cognitive science, nor do I think he is painting Pinker's own position fairly (though Lakoff claims the inverse as well).

3) This is classic Lakoff, and part of the problem:
1. He is threatened and is being nasty and underhanded -- trying to survive by gaining competitive advantage any way he can.

2. He is thinking in terms of old frames that do not permit him to understand new ideas and facts that do not fit his frames. Since he can only understand what I am saying in terms of his old frames, he can only make sense of what I am saying as being nonsense -- the opposite of what I actually say. That is, since the facts of what I am saying don't fit his frames, his frames stay and the facts are adjusted to fit his frames.

I guess Lakoff is saying that it is impossible for Pinker to understand him (or Pinker is an underhanded dastardly devil!). That's fine, but where do we go from here George? I mean, if he publishes in peer reviewed journals is it essential that only people with the correct frames see his work?

Let's hope some real cognitive scientists comment soon.

Read both essays.

Friday, October 06, 2006

Statistics & Derb   posted by Razib @ 10/06/2006 08:57:00 PM

Chris of Mixing Memory points me to two new statistics weblogs, Statistical Modeling, Causal Inference, and Social Science and Science Science Statistics Blog. Also, Chris tells me he will soon post a review of some papers on visual perception of race, so check his blog in a few days. Meanwhile, Derb has a new article in The New English review. He is in classic Derb form, as he states:
Furthermore, a dreadnought is not a hydrogen bomb. As puny as the MME states may be militarily, culturally, and economically, nukes are, like the Colt 45 in the Old West, equalizers. If, after a careful and judicious weighing of all the evidence, we were to conclude that there was no more than a ten percent chance of a terrorist nuke attack on a U.S. city over the next twenty years-that, in other words, the Sailer/Cochran hypothesis is probably correct, with probability at the 90 percent level-all the doom'n'gloom of Peters, Kurtz, the War Nerd, and me would still be fully justified.

Ten percent is alarming. Frankly, one percent is alarming. My own personal estimation is considerably lower, but what do I know? But, I do have a suspicion that if expectation of the probability of a nuclear attack on a U.S. city within the next 10 years is x, the likelihood that such an attack will occur in the Middle East is considerably higher, perhaps an order of magnitude greater than x.

Thursday, October 05, 2006

Glowing channels shed light on plasticity   posted by rosko @ 10/05/2006 09:46:00 PM

I'm sure Coffee Mug can explain a lot more about the significance of this, but in a new article in Science researchers report fusing a fluorescent protein to a particular potassium channel, known as Kv1.1, and using this to determine the site of synthesis of the channel. The particular type of fluorescent protein they used has one neat property that made this task a lot easier. When synthesized it has a green color, but when excited by UV light in the right way, it becomes red. Therefore, the protein made before and after this "photoconversion" process can be distinguished. It was found that the Kv1.1 that appears in the membrane in dendrites is synthesized locally, within those dendrites, rather than in the cell body. In addition, it was found that activation of the NMDA receptor dramatically decreased the rate of local synthesis of Kv1.1 This effect was found to be dependent on a protein called mTOR, which gets its name from its interaction with the drug rapamycin (which in fact is a well-known immunosuppressant, although it sounds like something you take to keep loud, rhythmic music from making you sick).

What could be the significance of this local down-regulation? Well, those of you with a background in neurophysiology will know that potassium channels hyperpolarize neurons, making them less likely to fire an action potential. Also, NMDA receptors are excitatory and seem to play a role in learning and memory. By shutting off production of potassium channels, the stimulus registered by the NMDA receptor can be reinforced, leading to potentiation of the dendrite's response.

The Wizard of Woz   posted by Razib @ 10/05/2006 09:23:00 PM

Steve Wozniak (inventor of the personal computer) was interviewed today on the radio show On Point. Nerds should check it out, he's a really interesting & entertaining fellow, though it seems he has some form of Asperger's (e.g., he keeps talking how he's just such a great engineer! All true of course, but a more socially aware person would cultivate a bit more false modesty). Also, In Our Time returned this week with a show about the Andalusian philosopher Averroes, who was such an influence on the Aristotelian Renaissance.

Cultural Differences   posted by Razib @ 10/05/2006 07:58:00 PM

Steve points me this post, Observations on Arabs. The author, an anthropologist by training, has 12 of them. Interesting, even if you don't agree with all of them.

Update: speaking of "cultural differences," see below (hint: Wonder Woman + pole dancing + lots of guys with palsy [Uberbrown responds]):

(via UltraBrown)

I await the headline, "brown actor breaks his kneck trying to be expressive with dance." Is is me or do brown guys dancing joyously in unison seem kind of "gay."

Sequencing is hard   posted by JP @ 10/05/2006 12:50:00 PM

Both the Wall Street Journal and the NY Times report on the new X Prize Challenge:
The X Prize Foundation, sponsor of a widely noted 2004 award for developing a reusable rocket suitable for private space travel, says it is now teaming with a wealthy Canadian geologist to offer $10 million to any team that can completely decode the genes of 100 people in 10 days.

And that's not all. As an encore, the winning team will be paid $1 million more to decode another 100 people's genes, including a bevy of wealthy donors and celebrities. Already accepted for future decoding: Google Inc. co-founder Larry Page, Microsoft Corp. co-founder Paul G. Allen and former junk-bond king Michael Milken.

John Hawks has a little commentary, including the ever important question: how does anyone actually know the winners get it right (as opposed to generating random variations on the current reference sequence, for example)?

One broader question overall is: why do we need a new method for sequencing? Sanger sequencing has gotten us this far, shouldn't a little more miniaturization and automation get us where we need to be? The answer, in a word, is no.

As I see it, the problem with both 454 sequencing (one of the top candidates to be the next major sequencing technology) and Sanger sequencing is their ability (or lack thereof) to handle large repeats. Here's what I mean:

First, note that sequencing is not the same as looking at a DNA molecule and reading on down. Sanger sequencing gets you about 600 bases at a time, so you first need to break the genome up into pieces of that size, sequence them all, then put them back in order. In 454 sequencing, you break the genome up into piece of about 1000 bp, but you only can read about 200 of them. Note that the human genome is composed of somewhere around 3.3 billion bases.

Now imagine you have a stretch of 3000 bases on chromosome 5, and another identical stretch on chromosome 11. If you're sequencing 600 bases, you have no idea that there are two copies of that sequence in the genome-- all you see is a bunch of identical sequence. The only thing you can do is sequence the same genome over and over again and hope that one of your 600 bp reads overlaps both some unique sequence from one chromosome and some of your repeat, allowing you to anchor it down. Of course, there are computational methods for resolving repeats that have gotten much better in the past few years, but the larger the repeat, the harder it is, and you still have to generate a lot of sequence-- off the top of my head, I'd guess you need something like 10X coverage (meaning for a 3.3 billion bp genome, you have to sequence 33.3 billion bases) to successfully resolve most repeats. That's a lot.

And this is not just a theoretical problem-- the reference genome is still not complete due to the presence of large repeats! And these things are important-- one, their architecture predisposes to pathogenic rearrangements and two, normal copy number differences in humans is a relatively unexplored source of natural variation.

In the short term (ie. in the next 2-3 years), no sequencing technology will be able to get around this problem reliably enough to win this prize. What we will see, however, is the use of array-based methods to type almost all polymorphism in the genome, which will give an approximation of a genome sequence. These technologies are cheap and fairly computationally tractable, meaning they can be widely used, but they're still subject to problems like the ones described above, so they're not as good as a full sequence.

In the long run, however, sequencing will indeed be routine. How long? I'm guessing no more than 10 years. And what technology will do it? My money is on technologies that work with a single DNA molecule. If they get good enough (and they will), it should be possible to simply read down a DNA molecule as if it were an open book. No problem with repeats there. Here's a paper that follows an enzyme down DNA and uses the movement of the enzyme to call the base. Nanopore sequencing has also gotten a lot of press in the last few years; I wouldn't be surprised if a company using that technology throws their hat into the ring.

It's worth noting that the vast majority of DNA variants in the world are singletons-- that is, they only appear in one individual. Once sequencing is routine, there will be a revolution in how we understand the genetic basis of phenotypes-- whether pathological or not.

Fisher Quotes   posted by DavidB @ 10/05/2006 05:49:00 AM

I just found a useful compilation of quotes from R. A. Fisher here, selected by A. W. F. Edwards.

While reading Fisher's published correspondence I also came across a couple of interesting passages on the subject of race. As they are not widely known I will give them in full. First, a letter from Fisher to P. de Hevesy, dated 28 September 1945:

Of course, I agree and agree strongly that one of the great human problems before mankind is to live in amity with other somewhat different inhabitants of the same planet. Mankind as a whole certainly constitutes a single family, and it is an old ideal and certainly not a dead one to treat all mankind as our brethren. I do think, however, that it is an essential part of the problem which, if ignored, will prevent us from solving it, if we do not recognize profoundly important differences between races, or if we imagine erroneously as to believe that such differences are rapidly disappearing through race mixture. By profoundly important differences, I mean, of course, not the superficial indications provided by skin and hair, but temperamental differences affecting the moral nature.... I should like you to recognize, if you agree, that it will be for us to regard other men with brotherly affection, and as in some senses, equal inhabitants of the world, without fostering what may be a dangerous illusion that we are equal in all respects, or discourage [note 1] earliest [note 2] enquiry as to the nature of racial differences, and without assuming that racial admixture is necessarily a step in the right direction, however much, assuming it could be accomplished in, say, ten thousand years, its accomplishment might seem to simplify world problems.

Note 1: 'discourage' is not grammatical; presumably it should be 'discouraging'.

Note 2: the printed text has 'earliest', but 'earnest' would make better sense. It is not likely that in September 1945 Fisher would be advocating research into racial differences as an 'earliest' priority. Fisher's handwriting was minuscule, and could easily be misread.

The other passage is in a letter from Fisher to Julian Huxley dated 27 November 1934, thanking him for three 'papers on Race', presumably written by Huxley. Some of Fisher's comments seem strangely reminiscent of more recent controversies!

I am glad you mention community of ancestry, which I think is an essential measure of racial similarity and, indeed, of genetic similarity when applied to groups, rather than to individuals. However, there is room for difference of opinion even there.

I cannot think that in view of their racial tradition, our Hebrew brethren will find any permanent response [note 3] in the conclusion that the word 'race' has lost any sharpness of meaning, or that it is hardly definable in scientific terms, ideas which seem attractive, only, I fancy, in the framework of current controversy.

Note 3: the printed text has 'response', but I think 'repose' would make better sense.

Source: J. H. Bennett (ed.): Natural Selection, Heredity and Eugenics, Including selected correspondence of R. A. Fisher with Leonard Darwin and others. 1983.

Wednesday, October 04, 2006

Second Nobel for Gene Expression   posted by the @ 10/04/2006 11:25:00 PM

The Nobel Prize in Chemistry goes to Roger D. Kornberg "for his studies of the molecular basis of eukaryotic transcription".

First, something entertaining: on The NewsHour, when asked to speculate about why Kornberg is a second generation Nobel-winner, the answer given by the senior Kornberg was "genes", and this was echoed by the Junior Kornberg as being at least one explanation.

Second, something maddening: Fire, Mello and Kornberg were all constantly asked by reporters how/whether their discoveries would lead to new medicine, yet each was awared for work at the most basic level of science. Thus asking them about medicine is a little like asking the physics winners if their discoveries would lead to starships. (In that the obvious answer is that it no doubt will contribute, and that the specifics are generally too complex or unclear to communicate to a general audience in a sound bite.)

Science and engineering 527 group   posted by the @ 10/04/2006 05:33:00 PM

In the NYTimes: Scientists Form Group to Support Science-Friendly Candidates

The group: SEA, Scientists and Engineers for America

They endorse an admirable set of principles -- if only they could be applied universally.

Selection for more muscle?   posted by JP @ 10/04/2006 04:48:00 PM

Via Dienekes comes this preprint [pdf] of a paper arguing for an ongoing recent selective sweep in the gene encoding myostatin, an inhibitor of muscle growth. The evidence for selection is based on resequencing of the gene in 146 people, which allows them to perform full-sequence-based tests for selection. They also look at the surrounding haplotypes, which are suspiciously long around the derived alleles (thus hinting at selection).

They speculate that the amino acid changes they find might lead to downregulation of the protein, thus leading to increased muscle mass. Notably, these variants seem to only have a large hold in Sub-Saharan Africa. I put the frequency figure below the fold. It's hard to see; I imagine a better figure will be in the published article.

Update from Razib: First,
In general, any mutations that increase the binding affinity between the propeptide and the mature peptide could generate a relative deficiency of myostatin activity. One of the many possible adaptive implications of such an effect could be protection from muscle-wasting in times of famine, a potentially recurrent phenomenon for early agricultural societies.

Weak!!! If protection against famine is where its at how about some buff-luv for the brownz???

Since the map sucks, here is the raw data (FYI, the Makranis of Pakistan have non-trivial African ancestry because of the Muslim slave trade)
Bantu N.E., Kenya (12: 29%, 25%)
Bantu S.W., South Africa (8: 6%, 31%
Mandenka, Senegal (23: 24%, 20%)
Yoruba, Nigeria (24: 8%, 19%)
San , Namidia (7: 0%, 14%)
Mbuti Pygmies, Democratic Republic of Congo (14: 4%, 29%)
Biaka Pygmies , Central African Republic (36: 8%, 14%)
Mozabite, Algeria (Mzab)(29: 2%, 2%)
Orcadian, Orkney Islands (15: 0%, 3%)
Adygei, Russia Caucasus (17: 0%, 3%)
Russian, Russia (25: 0%, 0%)
French Basque, France (24: 0%,4%)
French, France (27: 0%, 2%)
North Italian, Italy (Bergamo) (14: 0%, 0%)
Sardinian, Italy (28: 0%, 7%)
Tuscan, Italy (8: 0%, 6%)
Bedouin, Israel(Negev) (48: 0%, 5%)
Druze, Israel (Carmel) (47: 0%, 1%)
Palestinian, Israel(Central) (49: 1%, 9%)
Balochi, Pakistan (25: 0%, 4%) Brahui, Pakistan (25:2%, 2%)
Makrani, Pakistan (25: 0%, 12%)
indhi, Pakistan (25: 0%, 4%)
Pathan, Pakistan (24: 2%, 0%)
Burusho, Pakistan (25: 0%, 4%)
Hazara, Pakistan
(22: 0%, 0%)
Uygur, China (9: 0%, 0%)
Kalash, Pakistan (25: 0%, 0%)
Han, China (43: 0%, 1%)
Dai, China (10: 0%, 0%)
Daur, China (10: 0%, 0%)
Hezhen, China (10: 0%, 0%)
Lahu, China (10: 0%, 0%)
Miaozu, China (10:0%, 0%)
Oroqen, China (10: 0%, 0%)
She, China (10: 0%, 0%)
Tujia, China (8: 0%, 0%)
Tu, China (10: 0%, 0%)
Xibo, China (9: 0%, 0%)
Yizu, China (10: 0%, 0%)
Mongola, China (10: 0%, 5%)
Naxi, China (10: 0%, 0%)
Cambodian, Cambodia (10: 0%, 0%)
Japanese, Japan (30: 0%, 0%)
Yakut, Siberia (24: 0%, 2%)
Melanesian, Bougainville (22: 0%, 0%)
Papuan, New Guinea (17: 0%, 0%)
Karitiana, Brazil (24: 0%, 0%
Surui, Brazil (21: 0%, 0%)
Colombian, Colombia (13: 0%, 0%)
Maya, Mexico (24: 0%, 0%)
Pima, Mexico (25: 0%, 0%).

Boobs + Hezbollah = vapid...but   posted by Razib @ 10/04/2006 12:02:00 AM

O believers, look upon the depilated houri!

This has to be watched (and listened) to be believed. We are a marvelous species indeed....

"The Arab culture, the cigarette is part of it..."

Like, yeah!

(These are Canadians by the way, or as we like to say, excess North Americans)

(via Ali)

Tuesday, October 03, 2006

Radial unit hypothesis   posted by Coffee Mug @ 10/03/2006 09:53:00 PM

Pasko Rakic (cited in the Lahn paper that JP just linked) has studied the role of programmed cell death (apoptosis) in determining the complexity of the mammalian neocortex. The neocortex is the outer shell of your brain, has a six-layered structure, and has ten times the surface area in humans compared to macaques. When brains get that much surface area they have to become convoluted and get all those gyri and fissures that make it look like a bowl of noodles. Mouse brains are, by contrast, smooth. However, when Rakic and colleagues knocked-out the caspase-3 and caspase-9 genes in mice (the former being identified as *hot* by Lahn) their brains got all noodly. There is obviously more to it than this however because the mice weren't supergeniuses. I think they died pretty quick actually.

This all relates back to Rakic's radial unit hypothesis of cortical development and evolution. During corticogenesis, cells that are destined to be neurons are produced by asymmetric division of radial glia cells. You might describe the fated neurons as budding off the radial glia mother cell. Radial glia are named thusly because they have long processes that radiate out from the neuronal birth area closer to the middle of the developing brain and attach to the outer areas where the neocortical cell layers will form. Like so:

When the neuron is born it grabs onto the radial glia and starts climbing. It climbs past previously born neurons, so the neocortex develops in an inside-out fashion. Neurons that climbed up the same radial glia end up as part of the same functional unit, perhaps even acting as one big electrical component, since they are more likely to be connected by gap-junctions.

Rakic proposed that the size of the neocortex is determined by the number of radial units and thus the key developmental step for producing one of the most noticeable differences between humans and other primates will be radial glial proliferation. There are several factors that could affect the number of radial glia. I'll let him tell you what they are. Here is the free paper, skip to the last section:
A comparative embryological analysis of telencephalic development led to the proposal of the radial unit hypothesis of the ontogenetic and phylogenetic expansion of the cerebral neocortex at the cellular level (Rakic, 1988). According to this hypothesis, the expansion of the surface of the cerebral cortex is accompanied not only by the proportional increase in the number and length of RG cells, but also by the earlier onset of their differentiation, as well as an increase in duration of the G1 phase of the cell cycle and their longevity during individual embryonic development (Kornack and Rakic, 1998).
Recent experiments on embryonic brains in which the number of founder cells is manipulated by either the reduction of programmed cell death (Kuida et al., 1996; Haydar et al., 1999) or an increase in cell proliferation (Chenn and Walsh, 2002, 2003) support this hypothesis. In both cases the number of founder cells in the early VZ increases, resulting in a larger number of proliferative units that generate a corresponding number of radial minicolumns that enlarge the cortex in surface and create convolutions in the normally smooth (lissencephalic) mouse brain. Thus, an increase in the number of founder cells leading to the larger number of radial units in the neocortex is clearly correlated with the evolution of RG scaffolding.

Technology marches on...   posted by JP @ 10/03/2006 07:40:00 PM

The generation of data on biological functions has taken off exponentially in the past decade or so, and much of that is due to microarray technologies that allow thousands of experiments to be run in parallel. I love data, and the only thing that could possible entice me to get my hands wet in a laboratory is the possibility of generating a lot of it. So microarrays kick ass, but there's always been a sort of voodoo around it-- it's difficult to measure abolute levels of the RNA you're measuring (I get the impression things are more reliable when doing things like CGH with DNA), and things aren't always totally replicable from platform to platform or from lab to lab. Things have gotten better, of course, and they will continue to do so. From a perspective article in the most recent Genome Research:
[T]here is agreement that [mircoarray technology] ought to be able to detect RNA from small amounts of sample material, even single cells, in a way that faithfully represents RNA abundances. In addition, there would be advantages to describing abundance levels in absolute terms-numbers or molar amounts-rather than relative values, so that comparisons between genes and across many experiments can be undertaken. Furthermore, the dynamic range of microarrays should match the range of expression levels found in cells. Indeed, if the sensitivity, dynamic range, and quantitative nature of measurements could be improved, the current need for cross-validation with real-time PCR would become redundant.
The range of mRNA abundance levels in biological systems can approach 6 orders of magnitude, which clearly cannot be addressed by the ~10^3 dynamic range of current microarray experiments. In contrast, the Hesse investigators found the dynamic range of their single molecule detection system to be 4.7 orders of magnitude. In particular, the range at the lower end, at which regulatory molecules may be expressed, can be extended with greater confidence. It is possible that by using an appropriate single molecule microarray system, the full 6 orders of magnitude of biological expression levels can be addressed in a single readout.

Just something to whet your appetite...

Brains   posted by JP @ 10/03/2006 04:47:00 PM

Narrowing down genes that play a role in cognition, bit by bit...

1. Way back when, in 2004, Bruce Lahn's group published a paper arguing that nervous system genes, particularly neurodevelopmental genes, showed accelerated evolution in primates as compared to rodents. A new paper restricts the analysis to genes in a certain pathway-- one involved in programmed cell death-- and finds the same thing-- accelerated evolution in primates. A number of interesting genes worth study are in the pathway.

2. In April, a group reported on a (weak) association between intelligence and variants in a gene encoding for dysbindin-1. A new study sheds a little light on what this protein does and where it does it. A first step towards understand if and how it plays a role in higher cognitive function.

Monday, October 02, 2006

Worth reading....   posted by Razib @ 10/02/2006 09:15:00 PM

Chris at Mixing Memory has two posts on Mirror Neurons. Why are Mirror Neurons of interest? Go read what the brown dude has to say. Noah Millman has a definite read the whole thing post on Iran. The first comment is pretty ironic! Also, I've revisited the example of black and white twins on the other blog. This post got a lot of weird comments...some of which I had to delete. And of course, Reihan Salam's review of Idiocracy, the movie which synthesizes Beavis & Butthead and The Genetical Theory of Natural Selection.

Evolution on film   posted by agnostic @ 10/02/2006 08:00:00 PM

At his ScienceBlogs site, Razib has asked for suggestions for movies about evolution, other than your basic evolution vs. creation fare. I can't think of anything that has that grand of a theme, so I tried thinking of movies that highlighted a particular aspect of evolution that doesn't get taught much (whereas "we have a common ancestor with chimps" is commonly taught). At my personal blog, I wrote it up in more detail, but I thought Alien was pretty illuminating. Its plot is driven by one of the most important but least emphasized phenomena of recent evolutionary history: a population encounters an infectious organism that it has had no time to evolve a defense to, and which has apparently evolved in an arms race against some other population, and so faces damn near extinction. You might be exposed to this idea if you take a college course in history (then again, maybe not), but it's not given the importance it deserves, like being drilled into high schoolers.

What other movies are there like this, which purposefully or not showcase an important evolutionary dynamic in a way that even those who couldn't handle college-level courses could understand clearly?

AT --> GC mutations, recombination and selection   posted by JP @ 10/02/2006 07:31:00 PM

In the first comment on my last post, RPM brings up an interesting point, which I'm going to develop a little more here:

First, let's hypothesize that a non-protein-coding region of the genome is transcribed into some sort of functional RNA. As seen in the example of such an RNA on the left, the molecule has a secondary structure formed by the interactions of certain base pairs in the sequence, and that the interacting bases could be coded far away from each other. In proteins, amino acids that interact in the structure of the protein can evolve together. Perhaps there's a similar effect in the evolution of RNA genes.

If bases in an RNA molecule are to evolve together, this implies some sort of epistatic interaction between the two, in that a change in both sites is more fit than a change at only one site. However, the sweep of a beneficial mutation is greatly impeded by the presence of another beneficial mutation in the same area but on a different background, an effect known as Hill-Robertson interference. The only way multiple beneficial mutations can sweep to fixation together is if they're on the same haplotype, which can only happen if recombination brings them together.

Finally, note that recombination in a region is correlated with, and possibly causes, increased GC content in the region.

So, when Pollard et al. look for small (around 100 bp) regions with accelerated evolution in humans, they're essentially looking for small regions where a large number of mutations have gone to fixation. By the logic above, the only regions where this could possibly occur is in regions with high recombination. Further, regions with high recombination necessarily have a bias towards AT→GC mutations. So was their result (accelerated regions are found in areas of high recombination, most changes are AT→GC) a predicable outcome of their approach? Hindsight is 20-20.

Note that this is not at all an argument against these regions being under selection, just a comment that the only selected regions they should expect to find are a subset of all selected regions-- those with the specific properties noted above.

What drives accelerated molecular evolution?   posted by JP @ 10/02/2006 04:48:00 PM

In the paper describing the discovery of Human Accelerated Region 1 (HAR1), an RNA gene expressed in the brain and apparently under selection along the human lineage, the authors allude to the method they used to identify this region of the genome. The paper describing what they did in more detail is in revision at PLoS Genetics and is thus freely available.

Their basic approach was to find regions of the genome that were highly conserved throughout most of vertebrate evolution, but particulaly divergent in humans. To do this, they first aligned the chimp, mouse, and rat genomes to find highly conserved regions. They then looked at the genomes of 17 other species (including humans) and compare two phylogenetic models for each of the conserved blocks-- a model where the substutution rate is held constant to a model where an additional parameter for the human substitution rate is added. If the two models are significantly different, then voila, humans have experienced faster molecular evolution in that area.

They eventually come up with 202 interesting regions of the genome this way. The most impressive one they follow up a bit, as described previously. The regions they find are primarily non-coding, and located near genes involved in transcription and DNA binding. As is warranted, they give a nod to King and Wilson.

But have these areas really been under natural selection? One thing they note is that the substitutions they find are disproportionately AT-->GC mutations, and are located predominantly in areas with high recombination. Could the these substitutions simply be a neutral byproduct of the amount of recombination in these areas?

It's certainly possible, but one possibility, raised by a professor of mine, is that recombination hotspots aid the efficacy of natural selection. That is, in order for a number of benefecial mutations (which have arisen on different backgrounds) to sweep to selection with any efficiency, they must be on the same haplotype. The only way for two benefical mutations on different haplotypes to end up together? Recombination. So perhaps the presence of HARs in regions of high recombination is not an argument for their neutrality, but rather a hint as to the mechanisms that allow for strong positive selection on a region.

A Nobel Prize for gene expression   posted by rosko @ 10/02/2006 11:02:00 AM

The 2006 Nobel Prize in Physiology or Medicine goes to Andrew Z. Fire and Craig C. Mello "for their discovery of RNA interference - gene silencing by double-stranded RNA". This is the now quite well-known phenomenon of RNA interference (RNAi), in which double-stranded RNA can interact with complementary messenger RNA to block the expression of genes. This discovery was important as it showed how RNA can carry out a specific cellular function without having to be translated into a protein. Since then, there have been many other types of RNAs found to act as gene regulators, including the microRNAs (miRNAs) mentioned by Coffee Mug recently. Some of the protein players involved in RNAi, such as the enzyme Dicer, have been identified, but the mechanisms of action of all these RNAs, especially the more recently discovered types, are still quite uncertain.

Sunday, October 01, 2006

The unbreakable spell   posted by Razib @ 10/01/2006 08:07:00 PM

From The Shia Revival:
...Many nights during the war [Iran-Iraq War], Iranian soldiers would wake up to see a white-shrouded figure on a white horse blessing them. These apparitions of the Twelfth Imam were professional actors sent to boost morale. The common soldiers, often peasant boys raised in an atmosphere of simple piety, would then carry the tale to their relatives and friends in the villages and small towns they called home....

Extensive transcription in the fly   posted by JP @ 10/01/2006 02:54:00 PM

From a whole-genome tiling array study of transcription in Drosophila:

Many animal and plant genomes are transcribed much more extensively than current annotations predict. However, the biological function of these unannotated transcribed regions is largely unknown. Approximately 7% and 23% of the detected transcribed nucleotides during D. melanogaster embryogenesis map to unannotated intergenic and intronic regions, respectively. Based on computational analysis of coordinated transcription, we conservatively estimate that 29% of all unannotated transcribed sequences function as missed or alternative exons of well-characterized protein-coding genes. We estimate that 15.6% of intergenic transcribed regions function as missed or alternative transcription start sites (TSS) used by 11.4% of the expressed protein-coding genes. Identification of P element mutations within or near newly identified 5' exons provides a strategy for mapping previously uncharacterized mutations to their respective genes. Collectively, these data indicate that at least 85% of the fly genome is transcribed and processed into mature transcripts representing at least 30% of the fly genome.

The annotation of the human genome is probably not as good as in the fly, so the amount of unannotated genic regions is likely to be much higher.

Stuff that influences subjective well-being   posted by Coffee Mug @ 10/01/2006 01:40:00 PM

I always say I don't want to have kids because I don't want that much an anchor keeping me from doing important things, and I don't want my significant other's attention drawn away. Plus, I'm giving the finger to those genes for trying to manipulate me. I was arguing with my friend about whether this was rational as far as life satisfaction. Looking for data to shore my side up I found a report (pdf) about Marriage, Children, and Subjective Well-being. I'm not sure my side got shored, but it's interesting data:
Thus we find that:
(i) age exhibits the U-shaped relationship with life satisfaction found in multivariate
research employing large samples (with life satisfaction lowest at around 44 years
for men and 42 years for women);
(ii) life satisfaction is lowest for persons from a non-English speaking background,
especially women, and especially if their English language speaking ability is poor;
(iii) the effects of education on life satisfaction, while relatively small, are negative,
possibly the result of high aspirations that have yet to be met (Clark and Oswald
(iv) levels of life satisfaction are strongly affected by the presence of health conditions
and disabilities that limit activity;
(v) persons not in employment but who are actively looking for work (that is, the
unemployed) express the highest levels of dissatisfaction, while the most satisfied
are persons who are neither employed nor looking for work (so long as this
situation is not the result of poor health);
(vi) the presence of persons other than immediate family members in the household has
predictable effects, with children enhancing satisfaction of men but reducing it for
women, and adults enhancing satisfaction of women but not men;
(vii) satisfaction levels rise with household income per head, though the magnitudes of
the estimated coefficients suggest that the effect is relatively small and that very
large increases in income are required to raise life satisfaction scores by even one
point on the scale;
(viii) homeowners tend to be more satisfied with their lives than renters;
(ix) religion tends to be an influence that enhances life satisfaction;
(x) persons who are more forward looking in their financial planning and savings
behaviour are more satisfied, though the effect is only pronounced among women;
(xi) more stable home environments when young (as represented by living with two
parents at age 14) are associated with greater levels of life satisfaction.
• Couples are, on average, much more satisfied with their lives than single persons.
• Any difference in life satisfaction between married couples and cohabiting
couples is small and confined to long-standing relationships.
• Differences in life satisfaction between formerly married persons and other single
persons are only marked for women, and even then the reported life satisfaction
scores of most of these women have almost completely recovered to the level of
other single women by the time divorce is finalized.
• Remarriage appears to benefit men more than women, with the life satisfaction of
married men rising with each subsequent marriage. In contrast, women are no
more (or less) happy in a second marriage.
• Life satisfaction declines with the number of dependent children living at home
but rises with the number of adult children who have left home.
• Dependent children who live elsewhere have a depressing effect on life
satisfaction (though large standard errors mean relatively little confidence can be
attached to this result).
• The negative effects of young dependent children are very large for single parents
but non-existent for married mothers.