John Emerson has a long post up ruminating on the symbiosis between the humanities and the academy. John’s post appeals to me obviously, I certainly will never pursue a doctorate in the humanities or social sciences, but I have interests in Roman & Chinese history (my lack of fluency in other languages serves as a block on any scholarly contribution because of my first order ignorance of the primary literature). Some of the points John brings up will be familiar to those in the natural sciences as well, i.e., the perpetual post-doc ~ the nomadic adjunct. Our own David Nierengarten (Ph.D. biochemistry, Berkeley) expressed opinions that were not so far different from John’s in substance. I have a friend who is completing his doctorate in physical chemistry and now looking to go into the business management consulting world (merry X-mas B!).

Aftenposten, one of the leading newspapers in Norway, ran a story on Saturday about a study on birth weight and IQ conducted by Martha Gunn Eide, a researcher at the University of Bergen. (Eide is a medical doctor and this research represents her work toward a Doctorate of Medicine degree. Her thesis is entitled “Associations of Perinatal Conditions with Adult Body Size and Intelligence: A Register-based Cohort Study in Norway 1967-1999.”)

Below the fold are some highlights from the article (apologies for the rough quality of my translation!) >>

“Store babyer faar hoeyest IQ” [“Big babies get highest IQ”]

The birth weight of a newborn baby boy has significance for intelligence, course [success] and income….

[Martha Gunn] Eide defends in a few days her Dr. Med. degree at the University of Bergen. She has completed a very comprehensive study based on the combined data of nearly 400,000 male children.

“Are there grounds to believe there is a correlation between birth weight and IQ also in girls?”

“There is no call to believe that this would be appreciably different for girls,” says Eide, who is affiliated with The Department of Public Health and Primary Health Care, Faculty of Medicine at the University of Bergen.

Her study is based on information from the Medical Birth Register, Vernepliktsverket [compulsory military service department], the Statistics Central Bureau and the Rikstrygdeverket [Social Insurance department]. With this Eide has followed ca. 317,000 baby boys that were born in Norway between 1967-1979 through 18 years, as they met the [military] recruitment in period 1984-1999.

“The data are comprehensive facts analyzed for all boys in Norway over a 13 year period,” says the Bergen researcher, who has worked four years on the project.

5200 gram
…

“What we find is that birth weight is important for IQ. Higher birth weight, higher IQ,” says Kjell G. Salvanes [1], professor in Social Economics at the Norwegian School of Economics and Business Administration in Bergen….

Professor Salvanes has, together with two other international researchers, Sandra E. Black in Los Angeles and Paul J. Devereux in Dublin, investigated which factors are responsible for who takes higher degrees and get jobs with the highest pay….

godless discussed birth weight and IQ here while musing on C-sections as artificial selection.

[1] From the Cradle to the Labor Market? The Effect of Birth Weight on Adult Outcomes – Sandra E. Black, Paul J. Devereux, Kjell Salvanes

Reacting to this, I felt the need to point out that this is what a blastocyst looks like:

Those round things are individual cells. The zona pellucida is the human equivalent of an egg shell. The inner cell mass is the important part.

Dan Sperber (you can read many of his publications at his website) is an anthropologist based in France, whose work Explaining Culture, lays forth his ideas in regards to the “epidemiology of representations.”

1) If I recall correctly, you stated on an interview for EDGE that you became an anthropologist because of your confusion as to how people could be religious. Is this particular motivation common amongst anthropologists? In which case, it seems that France would have far fewer anthropologists than the United States!

I was brought up as an atheist but with respect for my Rabbinic ancestors and for religious thinkers of any persuasion more generally. The tension between these two attitudes was one of the causes of my becoming an anthropologist. People become anthropologists for a variety of reasons. I like the old line (I don’t know where I first heard it) that you have to be unhappy with yourself to become a (clinical) psychologist, unhappy with your society to become a sociologist, and unhappy with both to become an anthropologist. Be that as it may, I would be surprised if the number of anthropologists relative to the whole population were much different in France and in the US.

2) In EXPLAINING CULTURE you thanked John Tooby and Leda Cosmides for having inspired you somewhat in the direction you took. In ADAPTING MINDS by David Buller you are part of the prosecution against the Wason Selection Task as evidence for a ‘cheating detection’ innate facility. You have also defended ‘massive modularity.’ How would you characterize your own position in the alphabet soup of Evolutionary Psychologists, Behavorial Ecologists and assorted thinkers?

I always took for granted that an evolutionary perspective on mind and culture was correct, but it is Cosmides and Tooby who helped me realize that if was also potentially a very fruitful perspective. Even if I don’t care much about labels, I consider myself an evolutionary psychologist (part time; my main interest is in the epidemiology of representations, which draws on evolutionary psychology and other approaches). I agree on many essential points with Tooby and Cosmides, in particular the general idea – not necessarily the details – of massive modularity (I believe, actually, I was the first to use “massive” to describe modularity), but there are points of diagreement too. Among them there is a serious but also very local disagreement regarding their use of the selection task to test their hypothesis regarding the existence of a “social contract Darwinian algorithm.” It is an interesting and plausible hypothesis, but I believe that, in spite of all the work done by them and their collaborators, it has not been seriously tested so far because most of their evidence comes from the selection task, which, I have argued (in collaboration with Vittorio Girotto and others) is not a good test to study this or any form of human reasoning.

3) When I discuss with those with anthropological backgrounds the ideas I have encountered in your books (EXPLAINING CULTURE) and papers, or Pascal Boyer and Scott Atran’s books and papers, they seem confused and have little understanding of what I speak. Is your naturalistic paradigm more common among anthropologists in Europe than in the United States?

No, our common perspective (well illustrated also in the work of a few others, in particular Lawrence Hirschfeld – the four of us used to meet and discuss at my home in Paris in the early eighties) is still very much a minority view among anthropologists everywhere, as are all Darwinian views. On the other hand, I believe that our approach addresses maybe better and cetainly in greater detail than most other Darwinian approaches many legitimate concerns of people with a serious anthropological and ethnographic background.

4) In NOT BY GENES ALONE Peter Richerson and Robert Boyd refer to your work, positively. How do you feel about their project? Are they complementary, or addressing wholly different aspects of culture?

I have come to appreciate more and more the work of Boyd, Richerson, and their collaborators (in particular Joe Henrich). I believe our approaches are generally compatible, and our partly different focuses complementary.

5) It is often said that English is the language of science. How true does this seem in France? I notice that most of your work is available in English (or at least the work I know of!).

English is indeed the language of science. I don’t know whether native English speakers who don’t have to learn another tongue the way we do should be envied or pitied for that. As for my own work, most of it is written in English, or, when first written in French, translated into English.

6) Tooby and Cosmides tend to focus on the “psychic unity of mankind.” They argue that salient psychological characteristics must be monomorphic in our species because the tightly contingent nature of the organ would make polymorphism a suboptimal genetic architecture in relation to fitness, as recombination would destroy favorable genotypes. Other thinkers seem to lean toward an insertion of individual conditional (facultative) strategies as well as a mix of fixed evolutionarily stable strategies, taking a cue from the late J. M. Smith’s “hawk vs. dove” models. Where do you stand on this topic?

I don’t see these two approaches as incompatible. I do see insistance on the “psychic unity of humankind” and a focus on what humans have in common, including ranges of alternative strategies within populations, as essential both to the fruitful pursuit of an evolutionary approach to mind and culture, and to its acceptability in the broader scientific community. Would-be-scientific racism – which is still alive – has not contributed anything of genuine scientific value but has had the worse effect on the image of biological approaches to human affairs. So, I see it as both scientifically sound and responsible to starkly dissociate what we do from programmes that try to explain social and cultural differences among populations on the basis of biological differences.

7) Your work strikes me as rather pandisciplinary, and far more philosophical than much of what I am conditioned to expect from an anthropologist. Is this a function of your intellectual track, or a general cultural difference in how social scientists are trained in the Anglophone vs. Francophone worlds?

I was trained both in France and in Britain, and I have also learned a lot while being a visiting academic in the States. The specific mix of competencies and interests that you find in my work is an effect of my unquenchable curiosity and of the varied opportunities I have had to try and satisfy it.

8) EXPLAINING CULTURE was an anthology of your works, and I do not get the sense that it was directed toward a general audience. Can we expect a popular audience targeted
book for the English speaking market (it seems that Richerson and Boyd’s NOT BY GENES ALONE was just that)?

What I want to write is one or several books that will present the general picture I have in mind and of which I have so far aimed different fragments at different specialised audiences. The result should be more comprehensive, and I will try my best to make it easier than what I have written so far, but I am not sure my best will be good enough to appeal to a popular audience, however much I would like it to.

9) How do you view David Sloan Wilson’s arguments in regards to group selection and its role in fostering the evolution of altruism?

His contribution is well worth discussing, but I am not at all convinced by it, in particular because I believe that human cultures are far too labile to give much scope to cultural group selection (a point where I differ also from Boyd and Richerson).

10) If your parents hand emigrated to England, how do you think you would differ besides the obvious linguistic and culinary preferences and biases?

Sounds like you needed ten questions, and had only nine good ones. Seriously, I have no idea, and there are so many other things I would rather puzzle about.

What is evolution? I just had someone email me that people often ask him about his “belief” in evolution. This reiterates the point that people consider evolution a belief system, not a scientific paradigm. No matter how ridiculous it seems, how is it that we arrived at this juncture? There are multiple factors that have resulted in ~1/2 of Americans rejecting any form of evolution.

One important point is the reality that human beings as essentialists. That is, we imbue animals with essences. Elephants are elephants, even if you dress it up like a giant flamingo, there is something essential about elephants that is preserved. Paul Bloom would root this in our innate dualism. Others would elaborate in more detail aspects of innate derived folk biology. Children from Creationist and non-Creationist backgrounds tend to prefer narratives which imply immutable and essential natures to creatures all around them. As a point of plain fact that is what we see with our naked eyes. Whether or not evolution has shaped us toward a particular bias in regards to systemetizing about the natural world, the inputs we receive from the environment early on in development reinforce our conception of an ordered and discrete world where the essence of elephant is poured into the flesh of the proto-elephant.

This sort of thinking crops up in folk systematics (in mythologies about the beasts and birds and fish of the sea) as well as Creationist tracts which emphasize the importance of “kinds.” Obviously Creationists have problems with hybrids like mules, and in particular, fertile hybrids like female tigons. But it is not only Creationists who have problems with female tigons, biologists who espouse the biological species concept (BSC) also have issues with the reality of fertile hybrides (this is why the peculiar, at least intuitionally, phylogenetic species concept emerged [PSC]).

The BSC was promoted by the famous evolutionary biologist Ernst Mayr. Mayr also was a thinker in an older school of evolutionary phylogenetics which relied on the intuition and knowledge of specialists in particular clusters of species. The problem is that the BSC, that a species is defined by the bounds of fertile matings across a population generating fertile offspring is not workable across vast swaths of the tree of life. Not only do asexual creatures fall outside of the testable criterion of viable crosses between two individuals (unless you count various forms of horizontal gene transfer), but many traditional species generate fertile hybrids, and amongst many plants hybrid viability is so omnipresent as to make a joke of the BSC. The problems with the BSC and evolutionary phylogenetics resulted in the rise of the cladists in the 1960s, who emphasize the use of synapomorphies in determining monophyletic clades. A mouthful, huh? Cladists and the simultaneous rise of phylogenetic trees were welcome revolutions in turning systematics toward a more deductive and falsifiable set of methods. But the problem is that the hypothetico-deducative methods that lay at the root of these new fields are not necessarily intuitive. That makes sense, as I have said multiple times, human operational thought is not deductive, but abductive, we work from a set of facts to a good working explanation, we do not work from a hypothesis to predictions which we rigorously test.

There are rough & ready concordances between the intuitive phylogenies that were produced by Mayr’s school, and even Haeckel’s Tree of Life. For that matter, conventional human creation stories generate decent evolutionary relationships as well, they are clearly not random fabulations, but derive from a solid grounding in the data on hand. The problem is that science is a precise and reproducible system, and gestalt knowledge can usually only be resolved by appeals to authority and loud shouts of “You’re wrong, because I said so!” Despite the excessive fanaticism of cladists on shared derived characters, the rigor that they brought to systematics was certainly a good thing. And the challenge that they put forth to the BSC was also a good thing.

Because species are problems. Aside from species it is a traditional point of understanding that other taxonomical categories are arbitrary, i.e., genus (note that humans are not in the same genus as chimpanzees, though this does not make taxonomical sense). But even species can be problematic. This is an issue because the intuitions that we as humans have about species are, in my opinion, a major grounding for Creationist rejection of evolutionary theory. Once we dethrone species, intuition will no longer be the block it currently is. No longer will we have to appeal to the Talk Origins observed speciations page. No longer will we have to respond to the charge that there have been no observations of radical changes in body plan in one generation. No charges that “bacteria don’t evolve.” Ultimately these battles can be won, but the greater war is the sanctity of species, “kinds.”

Plant geneticists like Loren Rieseberg of the University of Indiana have been studying the importance of hybridization amongst various “species” for many years. Not only does a retrofit of Biblical systematics stumble upon the ubiquity asexual microorganisms, it is a poor representation of evolutionary genetic dynamics amongst the primary producers of biogenic matter on this planet, the plants. Unlike animals various plant species hybridize promiscuously, and one could say that for some taxa the term species is simply shorthand for correlation structure across space and time, interlaced by a continuity of gene flow.

But how relevant is this for animals? Clearly animals do not hybridize as easily as oak trees or sunflowers. Nevertheless, essentialist truths collapse with the insertion of slim needles. Species concepts are build upon a house of cards which assumes that populations which are so demarcated are (magically) insulated from affinal populations by mating barriers, whether it be prezygotic (behavior, mating season, etc.) or postzygotic (lower fitness of hybrids, hybrid sterility, etc.). But the intuitional concepts are grounded (more or less) in an absolutist model, not a graduated one. Like fucks like.

In How species evolve collectively: implications of gene flow and selection for the spread of advantageous alleles Rieseberg and Moran explore the importance of interpopulational gene flow in maintaining a rough species cohesion. Their contention is that advantagenous alleles of large effect can spread through a worldwide population via selection even when migration is not sufficient to homogenize neutral alleles. In short, Reiseberg and Moran save the species concept by suborning the impression that a species’ genetic architecture is a unitary and hypercontingent black-box which can not brook change or introgression. As I have noted before, t
he effect of gene flow on the distribution of frequencies across and within populations can be modeled with the equation 1/(4Nm + 1), where N is the population and m the proportion of migrants per generation. In short, Rieseberg and Moran argue that the rate of migration between populations within species is simply too low for genetic drift and local adaptation not to result in speciation. On the other hand, they argue that genes of large fitness effect may be able to spread even when the migration rates are not sufficient to equilibrate most of the genome. Recall that the probability of a mutation of fixation is 2s, and this can be translated into models which use migration in lieu of mutation to introduce genetic novelty. When s, the selection coefficient that defines the fitness of individuals with the allele vs. population mean fitness, is low, the probability of fixation is low, and random genetic drift is very powerful. But as s gets larger the probability of fixation increases and random genetic drift has a proportionately weaker role in the dynamics of frequency change. Rieseberg and Moran suggest that even on quantitative traits, where there are many loci, the locus of largest effect often explains a large fraction of variation, in which case the the alleles at these loci that confer great fitness will be able to sweep over worldwide populations and maintain species cohesion.

But the lessons to be learned from this paper extend beyond maintenance of putative species, they suggest the pluralism of microevolutionary mechanisms which are at work on the populational level. But we can take this further, in his paper The scale independence of evolution Armand Leroi expresses skepticism at the tendency for some to assert radically different dynamics on the macroevolutionary vs. microevolutionary level (i.e., clade level selection, etc.). He argues that there is a continuity between the two levels, microevolutionary forces of selection and drift are sufficient to explain taxonomical variety and novelty. This is an important point because it speaks to the idea that species and genus’ are not privileged, and despite their operational intuitional appeal we may need to move beyond innate systematics to understand how evolution actually works as a process. Rieseberg above argued that spread of alleles of large positive selective effect tie together species, but other work by plant geneticists shows that such alleles can spread across “species.” The essentialist concept of species is a fundamental block in the road to being open to this possibility. If species have peculiar essences sealed off from others it makes little sense that traits of one species would spread to another.

We privilege individuals and species as operational units because they are highly salient. Our minds are geared toward recognizing moving objects as individuals with agency. Faces are not simply smudges against the background, they stand out with particular detail. But in the broad scope of evolution individuals, and species, might not be as special as we believe. Certainly species are not intelligible in the context of asexual creatures beyond a gestalt level, and it is a highly problematic concept in plants as well. In concert with our tendency to think in terms of expanding non-reticulated genealogies, the species concept might be blocking our ability to understand the evolution of our own species. On the comment boards of this weblog someone expressed the idea that modern humans would simply not mate with neandertals because of physical differences. But the reality is that we know that humans have sex with ungulates. I believe what is happening is that we are abducing to the best possible explanation of the reality that we know we are special, and different. In their book Speciation H. Allen Orr and Jerry Coyne scoff at the possibility of human & non-human primate hybridization. This shows that even biologists are not immune from this bias when it comes to our own species. Orr’s work in particular has shown that mutations which generate fitness benefits of large effect can spread rather fast, and operate outside the conventional infinte alleles models (which assume fitness differences of very small effect). Rieseberg uses Orr’s work above as theoretical underpinnings for the paradigm that he is pushing forward.

In The Selfish Gene Richard Dawkins promoted a “gene centered” worldview that deemphasized individuals as “vehicles.” This was in the context of microevolutionary theories promoted by W.D. Hamilton which derived the evolution of altruism from the realities of kinship and gene identity. But just as genes brook no differences of individuals, that is, we are simply vehicles that they use to traverse space and perpetuate themselves through time, so species may also be simply more difficult valleys to cross. Though sexual reproduction in our species is banal, when viewed across the span of eons, one can not ignore the possibility that interspecies matings could also be a process which is highly relevant to the evolution as selectively favored alleles that introgress might spread like wildfire. Genes are discrete units of information on the nucleotide level, but from their vantage point the existence of creatures of flesh and cellulose might simply be continuous scaffolds which present non-trivial, but not insurmountable, barriers to traversion. So, in answer to questions relating to speciation, I’m not sure how ground shaking these points really are in the grand scope of evolutionary theory.

A fascinating paper just came out in Science, SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans. Heather L. Norton is one of the authors listed, so she knew very well what she was talking about when she suggested that there was far more to skin color variation than MC1R. Here is the eye popper from the text: “Based on the average pigmentation difference between European-Americans and African-Americans of about 30 melanin units (33), our results suggest that SLC24A5 explains between 25 and 38% of the European-African difference in skin melanin index.” I have pointed to models before which suggest ~4-5 loci that control skin color, this work does nothing to falsify that, but, it does show that between populations the variation in coloration in humans might be due to alleles of large effect which are differentially fixed. Evaluated over the whole species it is also certainly true that various alleles account for a different percentages of the genotypic component of variation, with many small effect modifier alleles likely hovering in the background of populations which are fixed for alternative alleles of large effect. Another important point is that the authors point out that both Africans and East Asians exhibit the ancestral allelic state, while Europeans are derived (a mutant descendent form), so the implication is that light skin is generated in East Asians by alternative genetic conformations. I have already pointed out that East Asians seem to be under strong selection, and moving toward fixation for Arg163gln MC1R allele (in contrast, Europeans are highly polymorphic for this locus). This points to the reality that evolution, or precisely, selection, explores a large phenotype & genotype space with multiple fitness peaks, and the expected outcomes might be random in nature when the options are constrained to the various peaks. The title of the post comes from the author’s observation that “This region [of the HapMap -R], which contains several additional SNPs with high-frequency differences between populations, was the largest contiguous autosomal region of low heterozygosity in the European (CEU) population sample…This pattern of variation is consistent with the occurrence of a selective sweep in this genomic region in a population ancestral to Europeans.” The low heterozygosity seems to be due to powerful directional selection which dragged a large number of adjacent SNPs within that haplotype block to fixation.

Finally, I want to add that this is a cool paper partly because of its broad methodological scope. Instead of just scanning the HapMap the authors also confirmed the developmental genetic expression via an animal model, zebrafish, which seems to exhibit the same variation in coloration on this locus as our own species. As they say, nature works with what it’s got, we’ve seen this with Foxp2, which shows up in derived form in humans, birds and whales (highly vocal species).

Anyway, the abstract:

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.

Here is an easier to digest piece in The Washington Post, Scientist s Find A DNA Change That Accounts For White Skin (the title isn’t true of course, there are East Asians with white skin). And Nick Wade is on it of course. Thanks to Abhi & Theresa for the tip. You can find a PDF of the paper as “whiteskin” in the forums.

Update: NPR has a nice summary. People seem interested in this topic.

Addendum: Check out William Saletan’s idiotic comment:

A single gene makes whites paler than blacks. Until 20,000 to 50,000 years ago, everyone was black; then a mutation in this gene created white people. Reactions: 1) Don’t talk about racial genetics; it encourages racism. 2) If color comes down to one gene, doesn’t that minimize its significance? 3) Did whiteness spread in Europe because it made people healthier, or because it made them more sexually attractive?

Saletan might have been tongue-in-cheek, but if he is he’s only perpetuating public stupidity (something that doesn’t need any reinforcement, thank you very much). First, less than half of the color variation even between Europeans and Africans is accounted for this gene, i.e., it is a necessary condition for “whiteness” (in the European sense), but it is not a sufficient condition. Living in an east coast metro area his model of a black-white dichotomy (i.e., the stories clearly suggest that East Asians lack the derived variant, but they aren’t black to my knowledge) in any conception of race pops up (if ($race != white) { $race = black}). Second, it makes the standard conflation of skin color with populational identity. This map makes it clear that skin color tends to track latitude far more than the combination of latitude & longitude that would imply a tight correlation with geographical populations. If you step outside the black-white world skin color can not predict populational identity very well (except perhaps at the very fair end of the range where Northern Europeans are alone). And as for reaction #2, what idiots actually said anything like this? That is a contention so bizarre that it seems to have been produced by a 3rd grader (I’m expectin
g to falsified as to the expectation of chronological age). I wouldn’t expect much from Saletan, but he writes the “human nature” column for Slate. How can I get a cushy gig like that???

Addendum II: Check out this post from a few years back on altitude adaptation to see what I mean about stumbling upon different fitness peaks via different strategies. Also, consider that many genes have pleiotropic effects, that is, they are implicated in a multitude of genetic pathways and influence many traits. There are many background assumptions operating when one says that locus x has fitness effect y on population z. Consider that perhaps light skin in the generality is a phenotype that is advantageous at higher latitudes, while dark skin is advantageous at lower latitudes. Since to the first approximation humans are creatures of Africa it makes sense that we would have fixed or constrained toward expression of genes that influence skin color toward a dark optimum. As non-Africans are a subset of Africans it seems plausible that the ancestral dark inducing forms of the genes will be shared. On the other hand, as the constraint for dark skin is released, because selection no longer favors it, the genes will start stumbling randomly in various directions via mutations. In the case of Europeans the MC1R locus seems to have walked in a random fashion and diversified greatly1 (30 alleles of greater than 1% frequency). On the hand, in East Asians the MC1R allele seems to have been selected toward one particular form that differs from the ancestral variant, in other words, constraint that limited the fitness toward those bearing the ancestral dark skin inducing allele(s) was released, but unlike Europeans selection now operated on a different allele and constrained diversification. This new finding makes that more intelligible: Europeans were given license to explore the range of MC1R variants because another locus was sufficient in hastening the induction of a light skin phenotype. Selection operates on genotype via phenotype, so the phenotype is sufficient to allow the individual to be fit and reproduce the genes, it is irrelevant what that particular conformation of genes that results in said phenotype is. An important point I am leaving out of this is that it is likely that MC1R has other fitness effects (recall the finding that redheads might be more sensitive to pain), and it is likely that this new locus is also implicated in other phenotypes, at least indirectly. In other words, loci don’t explore the fitness landscape by their lonesome, but only in the context of changes and conditions on other loci.

1 – Negative frequency dependent sexual selection is another way to generate diversity. Hard to falsify though, and usually neutrality is assumed to be a legitimate null hypothesis.

HOW E. COLI BACTERIUM GENERATES SIMPLICITY FROM COMPLEXITY

“In a surprise about E. coli that may offer clues about how human cells operate, the PNAS paper reports that only a handful of dominant metabolic states are found in E. coli when it is “grown” in 15,580 different environments in computer simulations.”

“When it comes to genomes, a great deal of complexity boils down to just a few simple themes,” said Bernhard Palsson, a professor of bioengineering at UCSD’s Jacobs School of Engineering and co-author of the study, which was made available online Dec. 15. “Researchers have confirmed the complexity of individual parts of biochemical networks in E. coli and other model organisms, but our large-scale reconstruction of regulatory and metabolic networks involving hundreds of these parts has shown that all this genetic complexity yields surprisingly few physiological functions. This is possibly a general principal in many, if not all, species.”

Similar principals have broad application.

1) Thousands of elements interacting in nonlinear dynamic feedback systems.
2) Evolutionary competition with survival of the fittest.
3) Subsets of elements operating together to maintain a specific state. Optimized to support that state.
4) States associated with successful survival strategies.

Applications in low-level neural circuits, high-level thought patterns, knowledge domains, belief systems, and social organizations.

Let’s work on knocking McConaughey off the main page. Here’s a quick summary of new stuff that just came out in PLoS journals. The full texts of each article are freely available.

1. Ablation of the Sam68 RNA Binding Protein Protects Mice from Age-Related Bone Loss.

Osteoporosis is a debilitating bone disease that is characterized by reduced bone mass and microarchitectural damage, which result in increased bone fragility and susceptibility to fracture. Peak bone mass, which is achieved by the age of 30 in humans, has been identified as a major determinant of resistance or susceptibility to osteoporosis. The authors generated mice deficient for the Sam68 RNA binding protein, a protein of unknown physiologic function. The mice develop normally and are protected against bone loss during aging. Age-related bone loss has long been associated with an increase in marrow adipocytes, which are derived from the same mesenchymal lineage as osteoblasts in bone marrow. The authors showed that Sam68 regulates the differentiation of this mesenchymal lineage, such that in its absence, osteoblasts continued to be generated in aging bone, leading to preservation of bone mass. This study identifies a physiologic role for Sam68 as a modulator of the bone marrow stem cell niche and hence of bone metabolism. The data identify Sam68 as a potential therapeutic target for the prevention and treatment of age-related bone loss.

Intersting bit in the disucssion about how heterozygous mothers kill 2/3 of their homozygous knock out pups.

2. The Flavoring Agent Dihydrocoumarin Reverses Epigenetic Silencing and Inhibits Sirtuin Deacetylases.

Sirtuins are a family of phylogenetically conserved nicotinamide adenine dinucleotide-dependent deacetylases that have a firmly established role in aging. Using a simple Saccharomyces cerevisiae yeast heterochromatic derepression assay, we tested a number of environmental chemicals to address the possibility that humans are exposed to sirtuin inhibitors. Here we show that dihydrocoumarin (DHC), a compound found in Melilotus officinalis (sweet clover) that is commonly added to food and cosmetics, disrupted heterochromatic silencing and inhibited yeast Sir2p as well as human SIRT1 deacetylase activity. DHC exposure in the human TK6 lymphoblastoid cell line also caused concentration-dependent increases in p53 acetylation and cytotoxicity. Flow cytometric analysis to detect annexin V binding to phosphatidylserine demonstrated that DHC increased apoptosis more than 3-fold over controls. Thus, DHC inhibits both yeast Sir2p and human SIRT1 deacetylases and increases p53 acetylation and apoptosis, a phenotype associated with senescence and aging. These findings demonstrate that humans are potentially exposed to epigenetic toxicants that inhibit sirtuin deacetylases.

Yeah… so that sucks. We don’t know and probably can’t find out easily whether this stuff accelerates aging, but I would prefer not to eat it. My guess is that DHC will probably just be labeled “natural flavors” in most foods.

3. Genome-Wide Associations of Gene Expression Variation in Humans.

With the finished reference sequence of the human genome now available, focus has shifted towards trying to identify all of the functional elements within the sequence. Although quite a lot of progress has been made towards identifying some classes of genomic elements, in particular protein-coding sequences, the characterization of regulatory elements remains a challenge. The authors describe the genetic mapping of regions of the genome that have functional effects on quantitative levels of gene expression. Gene expression of 630 genes was measured in cell lines derived from 60 unrelated human individuals, the same Utah residents of Northern and Western European ancestry that have been genetically well-characterized by The International HapMap Project. This paper reports significant variation among individuals with respect to levels of gene expression, and demonstrates that this quantitative trait has a genetic basis. For some genes, the genetic signal was localized to specific locations in the human genome sequence; in most cases the genomic region associated with expression variation was physically close to the gene whose expression it regulated. The authors demonstrate the feasibility of performing whole-genome association scans to map quantitative traits, and highlight statistical issues that are increasingly important for whole-genome disease mapping studies.

mRNA levels are a rich phenotype for doing association mapping because of microarray technologies. One problem is the question of what tissue to use. Blood is the easiest to acquire from large numbers of people, but of course that misses a lot of details.

4. Selective Constraint on Noncoding Regions of Hominid Genomes.

A major goal of human evolutionary biology is to understand what genetic changes make humans unique. One influential idea is that changes in gene expression are most responsible for unique human characteristics. Regulatory elements in noncoding DNA play a key role in controlling gene expression, so one approach is to study human–chimpanzee differences in these elements. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids. Contrary to some previous reports, these results argue that hominid noncoding regions are not evolving free of constraint.

This is in reference to previous reports that were less carefully done that found less conservation in human and chimp promoters than other mammals. That paper looked at large blocks of DNA, which are probably not functionally relevant. This paper looks at smaller blocks.

Just a reminder, with 10 days to x-mas/hanukkah, note that if you buy any books (to the right) via this website, or search for books via this site, we get a kick back. This also counts if you go into amazon via a session started through a click-through from this site.

I feel terribly remiss at not having posted on this earlier (!) — but last month People magazine named Matthew McConaughey ‘2005’s Sexiest Man Alive.’ Can’t say that I see it myself — although the Southern charm is quite — charming. (Of course, if you can pull Penelope Cruz, you probably got a lot more going for you than just charm.)

Maybe there is something about those Irish genes after all…. 😉

Update from Razib: Via Sitemeter I find out we are #1 for the Matthew McConaughey query on technorati (his name is hard to spell!).