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By Michael White | December 5th 2008 01:09 PM | 8 comments | Print | E-mail | Track Comments
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About Michael White

Welcome to Adaptive Complexity, where I write about genomics, systems biology, evolution, and the connection between science and literature, government, and society.

I'm a biochemist


... Full Bio

...the result is never pretty. I made this point in a comment, but I've hoisted it up here because this issue deserves more visibility.

Physics professor Steve Hsu makes this argument:

...you may have read the misleading statistic, spread by the intellectually dishonest Lewontin, that 85% percent of all human genetic variation occurs within groups and only 15% between groups. This neglects the correlations in the genetic data that are revealed in a cluster analysis. See here for a simple example which shows that there can be dramatic group differences in phenotypes even if every version of every gene is found in two groups (i.e., 100% of the variation is found within each group) -- as long as the frequency or probability distributions are distinct. Sadly, understanding this point requires just enough mathematical ability that it has eluded all but a small number of experts.)

This is a misrepresentation of what geneticists are claiming. It is absolutely true that 85-90% of genetic variation is found within populations (see this this recent paper in Science, and this short review in Nature Genetics for more discussion). That number is in fact calculated using differences in allele frequencies. No geneticist, Lewontin included, is claiming that 15% of all different gene versions are only found in single populations.

Hsu is correct in saying that it is the frequencies of alleles among different populations that are important, but he's wrong to claim that geneticists are missing this point. (People who study Higgs bosons aren't the only ones who know how to do principal components analysis.)

But the larger issue is whether these genetic differences add up to significant biological differences. Lewontin says no. Other geneticists don't go quite as far in saying there is 'no biological basis for race', but there are few that I am aware of who think that the between-population genetic variance prodcues major biological differences in our most complex traits.

To be fair, we should say that the jury is still out on how much phenotypic variation this population-specific genetic variation explains. Hsu places his bet:

Rather than proving that race is skin-deep, non-existent, or unimportant, modern genetic science is both proving that it is in fact existent, but also sets the foundation for the study of its true importance, which is probably somewhere in between the indifference of the sociologists and the hyperbole of the racists.

But in fact these genetic studies have not ruled out the idea that race is unimportant or skin deep. Yes, there are genetic differences, but whether these differences add up to anything more than superficial characteristics is still an open question. (The vast majority of genetic variants are very likely to be basically neutral variants.)

Hsu does lay out the question in another post:

Two groups that form distinct clusters are likely to exhibit different frequency distributions over various genes, leading to group differences.

This leads us to two very distinct possibilities in human genetic variation:

Hypothesis 1: (the PC mantra) The only group differences that exist between the clusters (races) are innocuous and superficial, for example related to skin color, hair color, body type, etc.

Hypothesis 2: (the dangerous one) Group differences exist which might affect important (let us say, deep rather than superficial) and measurable characteristics, such as cognitive abilities, personality, athletic prowess, etc.

A standard argument against H2 is that the 50k years during which groups have been separated is not long enough for differential natural selection to cause any group differences in deep characteristics. I find this argument quite naive, given what we know about animal breeding and how evolution has affected the (ever expanding list of) "superficial" characteristics. Many genes are now suspected of having been subject to strong selection over timescales of order 5k years or less.


The argument against hypothesis 2 is not naive, however it is naive to think that the selective pressures on human populations are anywhere close to the highly engineered selective pressures you find in animal breeding. And selection pressure isn't the only issue: there has been a fairly substantial amount of gene flow among human populations over the last 50k years, which tends to act against population differentiation. Given what we know about human population history, and the likelihood that a very complex trait like intelligence is controlled by many genes with pleiotropic effects, I find it implausible that significant differences in intelligence between populations have arisen over the past 50k years.

Hsu ridicules the "ever expanding list" of 'superficial' characteristics, but an expanding list is exactly what we should expect as we start to look at the genetic basis of traits. Superficial is a bad word perhaps; what really matters is not what's externally visible, but whether a trait can be influenced by a single (non-pathological) allele of large effect, which makes it easy to produce rapid and significant changes between human populations.

In the case of athletic prowess, you may have a single genetic variant that causes a major increase in athletic ability (here is an extreme example). Something similar appears to have happened with skin pigmentation in human populations that migrated out of Africa: single variants with a large effect on skin color was able to quickly reach high frequency in populations that moved out of Africa.

This is in contrast with intelligence: single genetic variants with large beneficial effects on intelligence are probably much, much harder to come by, because any large genetic change is likely to screw up something as complex as cognition. To get significant differences in intelligence between populations, my biological intuition is that you would need many small but non-negligible changes that together add up to something large enough to make a difference in the population distribution of intelligence.

In sum:

1. There are genetic differences between human populations, but genetic variance between populations is small compared to variance among populations.

2. We don't know how much of that minor amount of between-population genetic variance has an effect on phenotype.

3. Complicated traits, involving many genes with likely pleiotropic effects are, given human population history, much less likely to differ significantly (at least the genetic component) between different populations.

Comments

Michael,

I feel the need to correct several points made in your post.

This quote

"Rather than proving that race is skin-deep, non-existent, or unimportant, modern genetic science is both proving that it is in fact existent, but also sets the foundation for the study of its true importance, which is probably somewhere in between the indifference of the sociologists and the hyperbole of the racists."

Is not from me, but quoted from Dienekes' blog:
http://dienekes.blogspot.com/2007/04/prediction-of-continent-of-origin-u...

More importantly, you misread what I wrote about Lewontin. The sloppy claim that is often made (I think Lewontin may have known better and deliberately tried to confuse people) is that the 85-15 breakup of variance *implies* that we can't classify populations into groups or that there can't be significant group differences.

The 85-15 statistic in no way implies that there cannot be disjoint distributions of genes in two human sub-populations. That is illustrated here in pictures:
http://infoproc.blogspot.com/2008/11/human-genetic-variation-fst-and.html

When I wrote that the statistic popularized by Lewontin was misleading, I was specifically referring to this point. Note that Lewontin's name in the paragraph is a link to an earlier discussion of Lewontin's fallacy on gnxp (for some reason the link doesn't work now but this does:
http://en.wikipedia.org/wiki/Lewontin's_Fallacy ).

I've edited that paragraph for clarity; please tell me if it is easier to understand now:
http://infoproc.blogspot.com/2008/01/no-scientific-basis-for-race.html

The substantive scientific point is that even though the within group variance is larger than the between group variance (i.e., F_ST = .15), one cannot conclude anything from this -- there may be many directions in the space of genetic variation along which different populations are entirely disjoint. That is what the cluster studies are telling us, and what is illustrated here:
http://infoproc.blogspot.com/2008/11/human-genetic-variation-fst-and.html

*IF* position along the principal components identified in these studies is correlated with actual phenotypes, then we would see group differences.

On your blog you seem to quote the 85-15 result *as if* it actually implies something about phenotypical group differences or our ability to classify sub-populations genetically. If so, then you are an example of someone propagating Lewontin's fallacy. (But perhaps I misunderstand what you are trying to say.)

Certainly, the fallacy is widely accepted by many social scientists and biologists. It almost inevitably appears in discussions on these subjects.

adaptivecomplexity's picture
1. I apologize for misattributing the quote. It came from a paragraph that opened with a link to a previous post on your blog, so I mistakenly assumed the quote was yours.

2. You wrote that the 85-15% statistic is misleading, and that

This neglects the correlations in the genetic data that are revealed in a cluster analysis. See here for a simple example which shows that there can be dramatic group differences in phenotypes even if every version of every gene is found in two groups (i.e., 100% of the variation is found within each group)

The way you write this makes it sound like geneticists aren't considering differences in allele frequencies - that they are just saying 15% of the SNPs are population-specific. It's not true - this within-group/between group variance is determined by Fst or AMOVA, which do take into account correlations among genetic variants.

You call it a statistic popularized by Lewontin, but it's not - it's a significant result that's been featured over and over in key studies of the genetic structure of human populations, one that has held up well as researchers have moved from looking at dozens of synonymous sites in coding regions to hundreds of sites in repeat elements to hundreds of thousands of SNPs all across the genome. If you want to attack Lewontin's interpreation of it, that's fine, but don't treat this key genetic finding as some 'misleading' result popularized by Lewontin.

The question of just what this means for phenotypic variation is an open one, but Feldman, Lewontin, and King frame the issue well:

The classical definition of race, as applied to our species, is based on phenotypes such as skin colour, facial features and hair form that clearly differ between native inhabitants of different regions of the world. An underlying assumption is that all of these defining features (all largely genetic traits, although few of their genes have been identified) are characteristic of the genome in general. In other words, just as there are large differences between races in genes for skin colour, so there should be large genetic differences between races in general. In the previous absence of data to confirm or deny this assumption, it was not an unreasonable one to make.

But recent studies of genetic diversity indicate that the genes underlying the phenotypic differences used to assign race categories are atypical, in that they vary between races much more than genes in general. Together, the iconic features of race correlate well with continent of origin but do not reflect genome-wide differences between groups.

Note what they are not saying: they are not claiming that the 10-15% of between-population genetic variation is insignificant or meaningless. But it is true that these results are surprising, because they go against our everyday experience with visible, genetically controlled phenotypic differences between different populations.

Of course that still leaves the question of what impact the 15% of between-population variation means in terms of phenotype. You say that many biologists are promoting the fallacy that the 15% by itself has strong implications for phenotype, but as I read the literature, I hardly find any. Look at any of the major papers on this subject that have come out in the last few years, and the authors are careful to note that the genetic variance, in and of itself, doesn't tell you about phenotypic variance.

In theory, in the absence of other results, it could mean many different things.

But there is other knowledge to take into account. Given the nature of most SNPs (such as being in regions unlikely to be functional, or involving no change in a protein's structure), it's implausible that most SNPs would have much of an impact on phenotype, which means that much of the genetic variation we're talking about here has low-phenotypic potential. And much of the population structure of this genetic variation can be explained by genetic drift/founder effects.

Yes, of course some of the population-specific variation is driven by natural selection. It would be surprising if this were not true, because different human populations have adapted to different climates and food sources. But to compare the natural selection on human populations with animal breeding is absurd. Animal breeding involves extremely strong, directional selection for just a few traits. Human genetic variation is dominated by drift, and there has been substantial gene flow between various human populations for a long time.

Given that, I find it extremely implausible that racial differences in intelligence, as measured generally in developed countries with strong cultural factors, are due to genetic differences between populations. Intelligence has been under significant selection among all humans for a long time. Furthermore, the trait itself is likely to be easy to break - a change in one gene that produces dramatic changes one aspect of intelligence is likely to also have harmful effects, given the probable pleiotropy of many of the genes involved. This isn't proven, obviously, but it makes it, in my view, unlikely that strong natural selection would have rapidly driven an 'intelligence allele' (or set of alleles) to high frequency in one specific human population.

This is a mainstream view, informed by what we know from many areas of biology, not just studies of human genetic variance. Therefore, geneticist Lynn Jorde (who has been critical of Lewontin's statements that race, or at least population, has no biological meaning) is not promoting 'Lewontin's fallacy' when he writes:

A particular area of concern is in the genetics of human behavior. As genes that may influence behavior are identified, allele frequencies are often compared in populations. These comparisons can produce useful evolutionary insights but can also lead to simplistic interpretations that may reinforce unfounded stereotypes. In assessing the role of genes in population differences in behavior (real or imagined), several simple facts must be brough to the fore. Human behavior is complicated, and it is strongly influenced by nongenetic factors. Thosands of pleiotropic genes are thought to influence behavior, and their products interact in complex and unpredictable ways. Considering this extraordinary complexity, the idea that variation in the frequency of a single allele could explain substantial population differences in behavior would be amusing if it were not so dangerous.

jtwitten's picture
First, significant differences in the distribution of genetic variation between sub-populations do not imply significant differences in
phenotype distributions. 

Second, genetic markers can be used to identify geographic ancestry of individuals.  Geographic ancestry correlates imperfectly with traditional racial categorizations.  Therefore, the clusters do not actually equate to "races," unless we explicitly redefine "race" to make this so.  Pedantic, yes.  But, it is not possible to apply logic and reason to a problem without precise definitions of the terms being discussed.

From Hsu, as referenced above:
Hypothesis 1: (the PC mantra) The only group differences that exist
between the clusters (races) are innocuous and superficial, for example
related to skin color, hair color, body type, etc

Hypothesis 2: (the dangerous one) Group differences exist which might
affect important (let us say, deep rather than superficial) and
measurable characteristics, such as cognitive abilities, personality,
athletic prowess, etc.

I actually can't imagine formulating hypotheses like these for a number of reasons beyond the superficial rhetoric.  Significant difference

H0 (the result of random chance): Phenotypic distributions of sub-populations are indistinguishable.

H1: Phenotypic distributions of sub-populations are significantly different.

This formulation has several advantages.  First, they are testable and distinguishable.  Second, they are independent of highly subjective definitions of "importance."  Third, they are defined formally as opposed to in highly charged language that is only accurate in a limited time frame.  Less than a hundred years ago in many areas, Hsu's Hypothesis 1 was the "dangerous one" and Hypothesis 2 was the politically expedient one.  These alternative hypotheses can be tested for each new phenotype.

Having disproved H0, one would then need
to demonstrate that the significant difference in phenotypic distribution
between two sub-populations is due to genetic
variation not environmental variation.  The next step would be to show that the difference is not
consistent with genetic drift.  The population structure observed (essentially driven by that 15% intergroup variation) is broadly consistent with the effects of genetic drift (Jorde&Wooding 2004, Tishkoff & Kidd 2004, Novembre et al. 2008).  This would suggest that complex characters that are considered definitively human (e.g., intelligence and language) are unlikely to have been under strong selection over the evolutionarily short period of time since the Out of Africa migration.

adaptivecomplexity's picture
Less than a hundred years ago in many areas, Hsu's Hypothesis 1 was the
"dangerous one" and Hypothesis 2 was the politically expedient one. 


That's a great point.

adaptivecomplexity's picture
This is not quite on the topic of this post, and it's not one I've confronted head-on in this blog, but Greg Laden has an interesting discussion on his blog about race as a social construct:

These days, many people say that race is largely a social construct; while it may have a place in describing the population genetics of some species, is not particularly applicable to humans. I'm one of those people. The race concept is generally inapplicable or at best misleading when used as it often is with our species.

He's not saying this out of some desire to keep humans distinct from animals. The important point to take away from Greg's post is that human populations are much, much less distinct than many animal populations. Human populations have not been as isolated over the last 100,000 years as one might intuitively think. There has been a lot of gene flow among populations, which means that it's much harder to draw solid boundaries, using either genetic or phenotypic definitions.

Sure, you can pick study subjects likely to represent the most extreme genetic differences and show that they form distinct genetic clusters, but change your geographic sampling a little bit and you can find plenty of people to fill the space between the clusters. Lynn Jorde (who I cited in my original post) makes the same point. This is not always the case with many animal species. As Greg says, human populations really are genetically structured differently than say, wildebeest populations.

"This isn't proven, obviously, but it makes it, in my view, unlikely that strong natural selection would have rapidly driven an 'intelligence allele' (or set of alleles) to high frequency in one specific human population."

You may have discussed this elsewhere, but what's your take on the Cochran & Harpending paper on Ashkenazi Jewish intelligence?

http://homepage.mac.com/harpend/.Public/AshkenaziIQ.jbiosocsci.pdf

adaptivecomplexity's picture
I haven't posted anything extensive on this paper yet, and it deserves a fuller treatment than I've given it so far.

But my short answer is that the paper is largely speculation on correlation. The authors try to synthesize diverse genetic, psychological, medical, and historical data. The result is that they come up with an interesting hypothesis, but it's a hypothesis that is far from being verified or even thoroughly tested. In other words, this isn't really a study that establishes anything, it's one that puts forward a hypothesis. So it shouldn't be treated as a novel discovery.

That does not mean the authors can't be right - maybe they are, maybe there was very strong selection for intelligence on Jewish populations, but I think more plausible alternate hypotheses haven't been ruled out.

adaptivecomplexity's picture
There has been some discussion on the blogs of what I meant by this (for example, check out Gene Expression):

3. Complicated traits, involving many genes with likely pleiotropic
effects are, given human population history, much less likely to differ
significantly (at least the genetic component) between different
populations.

I want to clarify what I mean, because this sentence doesn't make it that clear (but previous statements in my post do get at my point more directly).

I'm trying to make a distinction between what geneticists call complex or quantitative traits (traits affected by different alleles of many different genes, with a quantitative range of phenotypes) , and something I would call a physiologically complex (or complicated) trait.

Complex or quantitative traits include both height and intelligence. But I'm arguing that something like height is not physiologically complex the way intelligence is.

Here is what I wrote in the original post:

[Something like height or athletic prowess] is in contrast with intelligence: single genetic variants with
large beneficial effects on intelligence are probably much, much harder
to come by, because any large genetic change is likely to
screw up something as complex as cognition. To get significant
differences in intelligence between populations, my biological
intuition is that you would need many small but non-negligible changes
that together add up to something large enough to make a difference in
the population distribution of intelligence.


So, for example, in the case of height, you can imagine that it is easy for a single allele of large effect to reach high frequency in a given population, resulting in a fairly tall (or short) population, which is basically what we observe.

I don't think that such a thing is very likely for intelligence, because, unlike the case of height, single alleles of large effect on intelligence probably also have large deleterious effects - something like intelligence is so physiologically complex that it is much easier to 'break' with a large-effect allele than something like stature, where an allele that extends how long growth plates in your leg bones are active is unlikely to also have major deleterious effects.

And to get race-specific differences, given current human genetic variation, you need single alleles with large effects - thus you have genetic differences in height and skin color, but not IQ.

This is essentially what Lynn Jorde says in the quote I posted in an earlier comment:

A particular area of concern is in the genetics of human behavior. As
genes that may influence behavior are identified, allele frequencies
are often compared in populations. These comparisons can produce useful
evolutionary insights but can also lead to simplistic interpretations
that may reinforce unfounded stereotypes. In assessing the role of
genes in population differences in behavior (real or imagined), several
simple facts must be brough to the fore. Human behavior is complicated,
and it is strongly influenced by nongenetic factors. Thosands of
pleiotropic genes are thought to influence behavior, and their products
interact in complex and unpredictable ways. Considering this
extraordinary complexity, the idea that variation in the frequency of a
single allele could explain substantial population differences in
behavior would be amusing if it were not so dangerous.

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