Drink whole milk, get pregnant

A story just came out today about drinking high fat vs. low fat milk, and the positive effect on fertility that the former can have. Remember the report that drinking milk increases twinning? Issues like this should be kept in mind when considering the spread of lactose tolerance, anything that increases fitness should spread. Why didn’t it? Well, it seems likely that cattle can’t be raised everywhere, so you have a situation where the selective benefit is geographically constrained. Also, modern lifestyles are characterized by no scarcity of calories so comparing this to pre-modern situations might be a false trail. The world wide spread of milk consumption should be changing things genetically though….

A note on the Common Disease-Common Variant debate

One of the more heated debates in human medical genetics in the last decade or so has been centered around the Common Disease-Common Variant (CDCV) hypothesis. As the name implies, the hypothesis posits that genetic susceptibility to common diseases like hypertension and diabetes is largely due to alleles which have moderate frequency in the population. The competing hypothesis, also cleverly named, is the Common Disease-Rare Variant (CDRV) hypothesis, which suggests that multiple rare variants underlie susceptibility to such diseases. As different techniques must be used to find common versus rare alleles, this debate would seem to have major implications for the field. Indeed, the major proponents of the CDCV hypothesis were the movers and shakers beind the HapMap, a resource for the design of large-scale association studies (which are effective at finding common variants, much less so for rare variants).

However, CDCV versus CDRV is an utterly false dichotomy, as I’ll explain below. This point has slipped past many of the human geneticists who actually do the work of mapping disease genes, and I feel the problem is this: essentially, geneticists are looking for a gene or the gene, so they naturally want to know whether to take an approach that will be the best for finding common variants or one for finding rare variants. However, common diseases do not follow simple Mendelian patterns– there are multiple genes that influence these traits, and the frequencies of these alleles has a distribution. A decent null hypothesis, then, is to assume that the the frequencies of alleles underlying a complex phenotype is essentially the same as the overall distribution of allele frequencies in the population– that is, many rare variants and some common variants.

This argument would seem to favor the CDRV hypothesis. Not so. The key concept for explaining why is one borrowed from epidemiology called the population attributable risk–essentially, the number of cases in a population that can be attributed to a given risk factor. An example: imgaine smoking cigarettes gives you a 5% chance of developing lung cancer, while working in an asbestos factory gives you a 70% chance. You might argue that working in an asbestos factory is a more important risk factor than cigarette smoking, and you would be correct–on an individual level. On a population level, though, you have to take into account the fact that millions more people smoke than work in asbestos factories. If everyone stopped smoking tomorrow, the number of lung cancer cases would drop precipitously. But if all asbestos factory workers quit tomorrow, the effect on the population level of lung cancer would be minimal. So you can see where I’m going with this: common susceptibility alleles contribute disproportinately to the population attributable risk for a disease. In type II diabetes, for example, a single variant with a rather small effect but a moderate frequency accounts for 21% of all cases[cite].

So am I then arguing in favor of the CDCV hypotheis? Of course not– rare variants, aside from being predictive for disease in some individuals, also give important insight into the biology of the disease. But it is possible right now, using genome-wide SNP arrays and databases like the HapMap, to search the entire genome for common variants that contribute to disease. This is an essential step–finding the alleles that contribute disproportionately to the population-level risk for a disease. Eventually, the cost of sequencing will drop to a point where rare variants can also be assayed on a genome-wide, high-throughput scale, but that’s not the case yet. Once it is, expect the CDRV hypothesis to be trumpted as right all along.

Recent Human Evolution in the house

Early man ‘couldn’t stomach milk’

Working with scientists from Mainz University in Germany, the UCL team looked for the gene that produces the lactase enzyme in Neolithic skeletons dating between 5480BC and 5000BC.
These are believed to be from some of the earliest farming communities in Europe.
The lactase gene was absent from the DNA extracted from these skeletons, suggesting that these early Europeans would not be tolerant to milk.

The paper will be Absence of the Lactase-Persistence associated allele in early Neolithic Europeans in PNAS. First LCT, then OCA2, and god knows what else? There is a limit in terms of what you can do with archeoDNA, but if the action went down in the last 10,000 years then it isn’t such a sweat.
One thing, the summary in Science is weird. Check it:

The culture-historical hypothesis is that, shortly after the domestication of livestock, a few lucky farmers with a genetic anomaly hit white gold: nourishment via milk. Then, according to this theory, natural selection took over and these lactase-persistent folks proceeded to populate much of Europe with their milk-guzzling offspring. A competing hypothesis argues that ancient Europeans domesticated milk-bearing livestock because lactase persistence was already quite common in certain populations.

Quite common? The area of the genome around LCT was hit by a hammer blow of selection less than 10,000 years ago, that’s why researchers use it to check if their methods for detecting selection are working. The fact that independent events of lactase persistence exist among other populations via alternative genetic architectures seems to indicate clearly the power of gene-culture coevolution. What’s up with Science doing a “look at both sides” framework when the evidence is so lopsided? I suppose selection could have been induced by a causative factor aside from milk, but I think we’re verging into Humean skepticism at this point, denying the ability to discern causality at all….
Carl Zimmer has much more….
Related: Lactose tolerance by a different stroke. Lactose tolerance/intolerance. Are multiple lactose tolerance mutations surprising? Genes & culture & milk. Lactose tolerance, is it “dominant”? Milk digestion, it does a body good.

CHRM2 and Intelligence

CHRM2 Gene Variants Associated with Intelligence

“Some of the participants in the study also took the Wechsler Adult
Intelligence Scale-Revised, a traditional IQ test. In all, members of 200
families, including more than 2,150 individuals, took the Wechsler test, and those results were matched to differences in individuals’ DNA.

By comparing individual differences embedded in DNA, the team zeroed in on CHRM2, the neuronal receptor gene on chromosome 7. The CHRM2 gene activates multitude of signaling pathways in the brain involved in learning, memory and other higher brain functions. The research team doesn’t yet understand how the gene exerts its effects on intelligence.”

Dick’s team is not the first to notice a link between intelligence and the CHRM2 gene. In 2003, a group in Minnesota looked at a single marker in the gene and noted that the variation was related to an increase in IQ. A more recent Dutch study looked at three regions of DNA along the gene and also noticed influences on intelligence. In this new study, however, researchers tested multiple genetic markers throughout the gene.

“If we look at a single marker, a DNA variation might influence IQ scores between two and four points, depending on which variant a person carries,” Dick explains. “We did that all up and down the gene and found that the variations had cumulative effects, so that if one person had all of the ‘good’ variations and another all of the ‘bad’ variations, the difference in IQ might be 15 to 20 points. Unfortunately, the numbers of people at those extremes were so small that the finding isn’t statistically significant, but the point is we saw fairly substantial differences in our sample when we combined information across multiple regions of the gene.”

Dick says the next step is to look at the gene and its numerous variants to learn what is going on biologically that might affect cognitive performance. Presently, she says it’s too early to predict how small changes in the gene might be influencing communication in the brain to affect intelligence, and she says it’s nearly certain CHRM2 is not the only gene involved.

Prior GNXP references to CHRM2:

Thompson and Gray: Neuroscience, genes, and IQ

More red meat

New blog posts

As a make-up for having hardly any time to post during the Week of Science, I have just added a set of four posts of pure science to my blog in rapid succession. On is on something that was already mentioned here, but the others are unrelated to anything on GNXP, so if you want to check them out, you can read them.

Posted in Uncategorized

Recent Human Evolution in the house

Early man ‘couldn’t stomach milk’

Working with scientists from Mainz University in Germany, the UCL team looked for the gene that produces the lactase enzyme in Neolithic skeletons dating between 5480BC and 5000BC.

These are believed to be from some of the earliest farming communities in Europe.

The lactase gene was absent from the DNA extracted from these skeletons, suggesting that these early Europeans would not be tolerant to milk.

The paper will be Absence of the Lactase-Persistence associated allele in early Neolithic Europeans in PNAS. First LCT, then OCA2, and god knows what else? There is a limit in terms of what you can do with archeoDNA, but if the action went down in the last 10,000 years then it isn’t such a sweat.

One thing, the summary in Science is weird. Check it:

The culture-historical hypothesis is that, shortly after the domestication of livestock, a few lucky farmers with a genetic anomaly hit white gold: nourishment via milk. Then, according to this theory, natural selection took over and these lactase-persistent folks proceeded to populate much of Europe with their milk-guzzling offspring. A competing hypothesis argues that ancient Europeans domesticated milk-bearing livestock because lactase persistence was already quite common in certain populations.

Quite common? The area of the genome around LCT was hit by a hammer blow of selection less than 10,000 years ago, that’s why researchers use it to check if their methods for detecting selection are working. The fact that independent events of lactase persistence exist among other populations via alternative genetic architectures seems to indicate clearly the power of gene-culture coevolution. What’s up with Science doing a “look at both sides” framework when the evidence is so lopsided? I suppose selection could have been induced by a causative factor aside from milk, but I think we’re verging into Humean skepticism at this point, denying the ability to discern causality at all….

Carl Zimmer has much more….

Related: Lactose tolerance by a different stroke. Lactose tolerance/intolerance. Are multiple lactose tolerance mutations surprising? Genes & culture & milk. Lactose tolerance, is it “dominant”? Milk digestion, it does a body good.

Buddhism, a religion or not?

The comments for the post where I imply that Sam Harris is a religiously inclined individual addressed the topic of whether Buddhism is a religion or not. This is a common issue, and I tend to cause some irritation whenever I declare that Buddhism is a theistic religion, because that’s not what you would read in books (or, Wikipedia). I’m generally a big fan of what books have to say, and defer to scholars in areas that I’m not familiar with, but, I’ve really come to the point where I simply don’t think that Religious Studies really adds enough intellectual value for me. Christians believe in the Trinity, Buddhists reject a Creator God, Hindus believe in reincarnation, etc. etc. But what does this really mean on the human level? Because I don’t really believe that supernatural belief systems have any reality outside of the minds of human beings. They are cognitive representations, nothing less, nothing more.
A little book titled Theological Incorrectness: Why Religious People Believe What They Shouldn’t, lays out most of the issues that I find of interest and curious about modal religious belief. The biggest one is that religious people don’t really take their axioms of belief and embed them into a chain of inferences guided by propositional logic. That is, secularists are always wondering why religious people who “believe” x nevertheless behave in ways 1…∞” that seem to contradict their avowed beliefs. For example, when I read about Saudi men gang-raping a woman and videotaping it, when they believe in a just and merciful God that is observing this, one has to wonder what’s going on in the human mind? Religious people regularly engage in this sort of psychology as well, “x couldn’t have been committed by Muslims, because Muslims don’t, by definition, do such things.” Or, “y wasn’t a real Christian, because if you really believed in God you wouldn’t behave in such a manner.” I’ve even seen strange definitions like “de facto atheists” for people who avow a belief in a divine entity but behave in an amoral fashion. Now isn’t that charming?

Read More

Academic Blogs directory

I noticed a post at Crooked Timber about something called The Academic Blog Portal. It’s a wiki. Both Gene Expressions are listed in the biology section. It is interesting to compare the representation of different disciplines, there are, for example, more linguistics and philosophy blogs than biology blogs, but also, more history blogs. Not all fields are represented to their proportion in academia, for example, only 4 engineering blogs.

The tactics of deceit

Over at The Edge the philosopher Daniel Dennett and evolutionary geneticist H. Allen Orr just had an exchange over Richard Dawkins’ The God Delusion. I am not particularly interested in the details of this debate, rather, on the front page this selection from Dennett’s letter caught my attention:

When I explained then in a private letter to you what I had meant, you conceded to me in your private response that you had not seen my point in the light I intended, and that my claim was not in fact the blunder you had said it was….

What could Dennett mean? I immediately thought back to this:

I did indeed misspeak (p. 126), but the result was ambiguity, not error. The issue is complicated: it depends on whether you’re measuring the (average) speed of departure from a starting point in genetic space, or the speed of attainment of some particular evolutionary product. I meant the former. [Dennett]

Now I’ve been in the population genetics business for some time and, frankly, I have no idea what Dennett is talking about. And-I can find no polite way of putting this-it’s hard to escape the conclusion that Dennett has no idea what he’s talking about, either. Even the most charitable interpretation I can come up with is just plain wrong. [Orr’s response]

Dennett’s phrasing was awkward and peculiar to say the least. Orr is an evolutionary geneticist who “was awarded the Dobzhansky Prize by the Society for the Study of Evolution and the Young Investigator Prize by the American Society of Naturalists.” In regards to a technical understanding of evolution Dennett was way out of his league. And only an analytic philosopher could confuse population genetic theory with such lexical opacity. That being said, I did not believe that Orr did not understand what Dennett was trying to say, unpolished though he was. This is how I unpacked it:

1) Because most mutations are deleterious, selection is generally a force for constraint, maintaining the ancestral state.

2) In contrast, random genetic drift operates upon evolutionarily neutral variation, so it exhibits (approximately) equal effect on mutants and ancestral alleles over the long term.

3) These insights lead to the contention of Kimura et. al. that most evolutionary change is driven by the substitution of neutral mutations, with random genetic drift a major engine. Even though the vast majority of neutral mutations go extinct, a small number perpetually substitute themselves over ancestral variants at a constant rate (i.e., the rate of substitution is proportional to the rate of mutation).

4) But, when there is a positively selected mutant, natural selection operates far faster in regards to fixing the variant than random genetic drift and stochastic processes might in the typical population size.

It is more complicated than that…but my point is that though Dennett wasn’t exactly clear, I think a reasonable observer could understand what he was getting at, or at least the somewhat confusing waters into which he had ventured. Orr did not acknowledge this. As I said, Orr is a world renowned evolutionary geneticist (as he implies in his response), so I was skeptical that he was as clueless as he’d let on.

So, when I read Dennett’s full letter, I was not surprised. Here is what he says:

You leveled very serious charges of error and incomprehension in that review, and when I challenged them, you responded with a haughty dismissal of my objections (in an exchange in the Boston Review). Quoting an example, dealing with the speed of evolution: “Now I’ve been in the population genetics business for some time and, frankly, I have no idea what Dennett is talking about. And-I can find no polite way of putting this-it’s hard to escape the conclusion that Dennett has no idea what he’s talking about either.”

Dennett is bringing up exactly what I remembered in The Boston Review! This was 10 years ago, but Dennett obviously still resents Orr mocking him. In private correspondence Dennett states that Orr admitted that he wasn’t really wrong, and Orr’s response to this new salvo from Dennett does not contradict that characterization.

I writing about this for one primary reason: I thought, at the time, that H. Allen Orr was striking a low blow dishonestly when he could have stood on firm ground, though with a weaker impact. I’ve thought about this exchange on & off for several years now, and have considered blogging it, because I think it is perhaps a reflection of H. Allen Orr’s character. Most of the readers of The Boston Review don’t spend their free time reading The Genetical Theory of Natural Selection or Motoo Kimura’s papers, they wouldn’t be able to parse from Dennett’s somewhat confused phrasing what he was trying to get at. In other words, assuming that Dennett wasn’t a moron they couldn’t really map his verbal exposition onto a range of evolutionary models, because it isn’t exactly as if a broadly educated person is familiar with the great Neutralist vs. Selectionist debate of the 1970s. They were relying on H. Allen Orr’s expertise. I just can’t believe that H. Allen Orr didn’t understand what Dennett was trying to say, or, that he couldn’t have seen what he was getting at if he hadn’t prejudged Dennett and his ideas as a whole. If I had been him I would have pointed out that Dennett’s graceless exposition of the relationship between neutral and selective forces in evolution should be a clue that the man doesn’t have the technical competency to engage in such an ambitious meta-project as the one he laid out in Darwin’s Dangerous Idea. Instead, Orr is implying that Dennett simply doesn’t know what he’s talking about, and making him out to be the fool. This is rhetorically far more powerful, and I am sure it persuaded most readers of The Boston Review, who are not going to be conversant in the details of evolutionary genetics and trust H. Allen Orr. After all, who are you going to listen to on this topic? A philosopher or an evolutionary geneticist?

To my mind Orr did a disservice to science and intellectual discourse. He went for the knockout, calling an intellectual ignorant is basically undermining their worth. Saying that they are a bit confused lacks a similar punch. But the readers of The Boston Review, or the lay audience in general, is not looking for a legal case where you are an advocate for your position at all costs, because science and intellectual discourse is more than one battle, it is a long war against our moral and personal failings, against pride, against ego, against self-interest and self-aggrandizement. Most of the battles are lost, but slowly the war grinds on and the trenches keep moving inch by inch. Ph.D. scientists make considerably less in income than their intellectual inferiors in law or medicine. But the field in which they operate is one of great prestige, of civilizational significance. Presumably they wish to engage in the adventure of the ages, at the cost of financial status. Scientists are human, as the politics which suffuses any university department would confirm, but, like monks meditating upon the nature of God, abjuring themselves of worldly pleasures and satisfactions, scientists have to err on the side of truth as they see it, and not a short term rhetorical victory. For what shall it profit a man, if he shall gain the whole world, and lose his own soul?

Addendum: Readers can follow the links and judge for themselves if Dennett wasn’t clear in his intent, even i
f he was being muddled about it. Perhaps Orr didn’t understand what Dennett was trying to say. But if Orr could comprehend the opaque prose in The Genetical Theory, I can’t see why he couldn’t parse what Dennett was trying to get at. And just to be clear, though I point a finger at Orr on this occasion, rest assured that I understand that we are all guilty of this particular sin, and that includes myself. I simply want to emphasize Orr’s transgression here because I think it is important for us to remember that no matter the satisfaction that victory in one battle gives us, we are not fighting without a long term purpose, and dishonorable victories are fundamentally Pyrrhic.

Addendum II: Also, I understand that in practice science between the bounds of accepted & rejected consensus is quite the bloodsport, and an adversarial & amoral dynamic is common. Though this injects quite a bit of “noise” into the system, I trust over the long haul that the scientific culture will beat expectation in modeling reality. That being said, the issue I am pointing to here is slight of hand by gatekeepers. Orr writes reviews books as an evolutionary geneticist, with all the expertise that that entails. His behavior in this case was repulsive to me because he sacrificed the chance to elucidate the nature of evolutionary change to a broad audience so that he could mock (in, I suspect, a dishonest manner) someone and so win a point in an exchange of letters. I will refrain from an evolutionary psychological analysis of how this was truly “rational” from Orr’s individual perspective….