recent selection

Ann Gibbons has a long news article in the current Science reporting on an interdisciplinary conference on recent human diet evolution ("What's for Dinner? Researchers Seek Our Ancestors' Answers"). The article covers a lot of ground, from Michael Richards' work on the isotopic signature of diet in early Upper Paleolithic people, to Bill Leonard's work on diet adaptations in Siberian reindeer herders, to Jonathan Wells' work on maternal nutritional status and epigenetics.

It's a good "why evolution matters to today's nutritional choices" article.

A section of interest to me:

The agricultural revolution favored people lucky enough to have gene variants that helped them digest milk, alcohol, and starch. Those mutations therefore spread among farmers. But other populations remained more carnivorous, such as the Saami of frigid northern Norway, whose ancestors herded reindeer. Among Saami ancestors, genes to digest meat and fat efficiently were apparently favored. One gene variant, for example, makes living Saami less likely to get uric acid kidney stones—common in people who eat high-protein diets—than are people whose ancestors were vegetarian Hindus and lack this gene variant, says geneticist Mark Thomas of University College London (UCL).

I'll have more on a similar topic later -- recent shifts in genes due to agricultural subsistence has become a favorite subject of local interest. One would think I might get some funding from the Wisconsin dairy industry for this, but nothing so far...

There is an unresolved tension in the article: Is there a better diet for everyone? Clearly some populations have undergone large recent diet changes with bad consequences; the same bad outcomes occur in some people despite possibly adapting to new diets for thousands of years. And yet, every metabolic or diet-related syndrome is variable, and we know that some genes related to digestion and metabolism have rapidly changed. "Westernization" is not as simple as it seems, nor is agriculture (or, for that matter, pastoralism) -- and the responses to each vary for stochastic reasons in different populations.

It's a good interesting complexity, in a field where simple categorical statements can get a lot of attention.

Time has a story about Stephen Stearns and colleagues' work characterizing ongoing selection using the Framingham Heart Study sample:

If these trends were to continue with no cultural changes in the town for the next 10 generations, by 2409 the average Framingham woman would be 2 cm (0.8 in) shorter, 1 kg (2.2 lb.) heavier, have a healthier heart, have her first child five months earlier and enter menopause 10 months later than a woman today, the study found. "That rate of evolution is slow but pretty similar to what we see in other plants and animals. Humans don't seem to be any exception," Stearns says.

I haven't had a chance to see the new study yet, and I'll do a little review when I get it. Jerry Coyne has some more information based on a preprint.

My students have heard me say many times that it would take a sample of thousands of people to test the hypothesis of neutrality within today's population. Well, Framingham is one such sample, and it's not surprising that some things would be found significantly to affect fitness.

The Time article mentions our work on recent evolution in a very positive way. Of course, the Framingham sample isn't suitable for testing what has been going on during the last 40,000 years; it is about mass selection on phenotypes in the present American population. That will involve mostly selection on standing variants, things that are already common in the population. Some of those may be things that were increasing in the past, others not -- some may even be reversals in direction compared to pre-industrial times. And there's no predicting how they might change in the future, as we continue to change our environment out from under ourselves.

I've seen a few comments that we shouldn't trust the sample because it's unrepresentative, too small, etc. I think people may be overlooking the fact that the Framingham Heart Study is bigger than the census sizes of many species in nature. You can detect selection on phenotypes in this sample, and they surely know the heritabilities of many of them. But I'll have to see the paper.

François Balloux (2009) has a polemic in the online access area of Heredity presenting references about mtDNA selection, and arguing that the use of this single genetic marker is no longer warranted without support from other loci.

Yay! I've been saying that both here, and in peer-reviewed articles, for several years. I think serious workers know that one gene is not enough; two genes (mtDNA and Y chromosome, for example) aren't enough -- we have to integrate information across every possible source, genetic, skeletal, and anthropological, to really test hypotheses about the past.

Still, an industry of mtDNA sequencing has grown up, reviewing each others' grants and papers, and shutting down any discussion of adaptive changes. Balloux's commentary addresses this problem -- I'm going to quote the same paragraph as Dienekes:

Let us assume I gave a seminar. I would tell the audience about my latest results on the population history of the pigmy shrew. My findings would be based on a stretch of DNA comprising several metabolic genes, showing no signs of genetic recombination. Armed with sequences from a large number of individuals sampled over a broad geographical area, I would make some inference on the colonization routes and times. To make life easier, I would restrict my analysis to the mutations I liked best, with nice names having been given to related sequences, rather than relying on dull mathematical quantities. As I reach one of the key conclusions of the lecture, which would go as follows: 'It is obvious from the distribution of haplotypes Amanda, Eugenie* and Hector_2 that the Outer Hebrides were colonised about 50,000 years ago, this was followed by considerable population fluctuations, a bottleneck during the last Ice Age, a swift recovery and a dramatic recent expansion over the last 200 years and...'. Imagine that, at that climactic stage I was interrupted by someone in the audience. The impertinent would say, 'Sir, can I just ask you whether this confidence in your conclusions may not be misplaced; your analysis is based on a single genetic marker, which comprises genes with a central role in metabolism and is thus likely to have been affected by natural selection'. An awkward silence may ensue, as I would find it difficult to dismiss this criticism easily.

Well, let me tell you, I've been in dozens of audiences, and have raised that exact point. Here is a sample of the bogus responses I've gotten to this question:

Bogus answer 1: There are no functional differences between humans and chimpanzees in the mtDNA, so it can't have been selected during human evolution. False, false false!

Bogus answer 2: Metabolic processes are highly conserved, and humans couldn't have changed much. Hello? Have you noticed that your breakfast didn't exist in the Paleolithic?

Bogus answer 3: But the pattern of variation can be equally explained by a bottleneck. Some aspects can, others can't so easily.

Bogus answer 4: We examined only noncoding parts of the mtDNA, so there could be no selection. Yes, believe it or not, this is the most common response. I guess they don't teach people about linkage anymore.

Bogus answer 5: There's little or no evidence of selection on any gene in recent human evolution. Human evolution may have stopped entirely. Oh, lord. Yes, I've gotten this one many times.

There have been others over the years. Yet mtDNA is a big business -- people seem to be worried that the slightest criticism will bring down the whole thing like a house of cards. That's not true, even if mtDNA has sometimes been selected during human prehistory or history, that doesn't mean it isn't a useful marker for many purposes. But many seem more comfortable avoiding the issue entirely.

I think that taking the hypothesis of selection seriously would improve most of the work in this field. The possibility of selection doesn't eliminate demographic interpretation -- for example, the high ancient African mtDNA variation allows us to test hypotheses about African demography before 50,000 years ago, and there the data appear to reject the hypothesis of selection, at least after around 150,000 years ago. Gene genealogies don't allow us to see the whole past, just the time and forces that they experienced. If we ignore one of the major forces, we are reducing our knowledge.

There is an obvious problem testing the hypothesis of selection with mtDNA. When we consider any one single locus, it's always possible to find some demographic scenario that yields exactly the same predictions as selection. It's just a mathematical necessity -- selection is fundamentally a demographic phenomenon, and the increase in frequency of selected alleles looks similar to exponential growth of a small population.

So what can we do? Fortunately we have lots of options. We can test the proposed demographic hypotheses against the historical record. When we make observations that show that people 1000 years ago had very different frequencies of common haplotypes, well, we know it was selection. There hasn't been any genetically significant bottleneck in the last 1000 years! When we see small Neolithic population samples dominated by haplotypes that are very rare today, again, no historically possible bottleneck could have caused that.

Balloux with his colleagues (2009) has shown that one aspect of mtDNA patterning -- the association of haplogroup diversity with geography -- is very unlikely to have arisen by genetic drift. Here's part of their abstract:

We show that populations living in colder environments have lower mitochondrial diversity and that the genetic differentiation between pairs of populations correlates with difference in temperature. These associations were unique to mtDNA; we could not find a similar pattern in any other genetic marker. We were able to identify two correlated non-synonymous point mutations in the ND3 and ATP6 genes characterized by a clear association with temperature, which appear to be plausible targets of natural selection producing the association with climate. The same mutations have been previously shown to be associated with variation in mitochondrial pH and calcium dynamics. Our results indicate that natural selection mediated by climate has contributed to shape the current distribution of mtDNA sequences in humans.

They took a dual approach to testing the hypothesis of selection. First, they modeled the evolution of haplotype diversity under neutrality, and showed that the empirical distribution lies significantly outside that range of results. But even so, we might imagine some bottleneck scenario that would cause low diversity in high-latitude peoples, and this would be difficult to refute historically because many of those populations have poor historical documentation. But demography should have similar effects on other genes, and they were able to show that the rest of the genome doesn't share the mtDNA pattern.

It's really not that hard to test demographic hypotheses, using comparative genomics and anthropological knowledge. That's what anthropological genetics should be doing more and more. There was a time when obtaining a reasonable sample of mtDNA was an accomplishment, and comparing that sample to other genes was not feasible. But that time is past, and hopefully the review process -- journals and grants -- will start demanding some integration of mtDNA phylogeography with results from the rest of the genome.

Back to Balloux's conclusion:

Exploiting these new resources of autosomal variation will present significant challenges, but it will not help overcoming them if a large fraction of the community of human population biologists persists in sticking to mtDNA as the marker of choice.

Mitochondrial DNA isn't the tip of the iceberg -- it's an ice cube on top of the tip of the iceberg.

Related:

"Mitochondrial DNA selection review"

"Mitochondrial DNA and sperm"

"mtDNA selection in Iceland?"

"Complete Neandertal mitochondrial sequence, and selection on human (not Neandertal) mtDNA"

"Did Neandertals need better mitochondria?"

"Has the dam broken on mtDNA selection?"

Mitochondrial DNA adaptations in living human populations"

OK, that's enough related posts. But you can find a whole lot more by searching the topic!

References:

Balloux F. 2009. Mitochondrial phylogeography: The worm in the fruit of the mitochondrial DNA tree. Heredity (advance online): doi:10.1038/hdy.2009.122

Balloux F, Lawson Handley L-J, Jombart T, Liu H, Manica A. 2009. Climate shaped the worldwide distribution of human mitochondrial DNA sequence variation. Proc Roy Soc Lond B 276:3447-3455. doi:10.1098/rspb.2009.0752

Everybody's noticing the new article in PLoS Computational Biology about lactase persistence, which I've been emailed from several readers. Thanks for sending it, everyone -- it's always helpful even if I get it more than once!

The short version is that the authors place the origin in Germany around 7500 years ago, and using a 2-d forward-time dispersal model, find that fits well with the distribution of allele frequencies in Central Europe.

There's only one little problem: It's hard to see how the same scenario gets the allele to India. Or, for that matter, Ireland. The authors posit that Indian lactase persistence will be found to be caused by a "diversity" of alleles. They seem to have missed this paper that found a greater diversity of lactase-associated haplotypes "north of the Caucasus" -- consistent with an initial steppe dispersal. OK, that's two problems, and they're not little.

Their potentially interesting finding -- the dispersal of lactase persistence in their model didn't increase the diffusion of other central European genes -- should inspire more modeling. How independent can a strongly-selected allele be of its genomic background? Can selection cause demographic events without affecting unlinked neutral variation? I imagine we can explore this issue with differential equations.

(see also, Dienekes, Yann Klimentidis, GNXP)

References:

Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG. 2009. The Origins of Lactase Persistence in Europe. PLoS Comput Biol 5(8): e1000491. doi:10.1371/journal.pcbi.1000491

Enatteh NS and 26 others. 2007. Evidence of Still-Ongoing Convergence Evolution of the Lactase Persistence T-13910 Alleles in Humans. Am J Hum Genet 81:615-625. doi:10.1086/520705

I couple of people have asked me about a new paper in PLoS Genetics by Graham Coop and colleagues, titled, "The role of geography in human adaptation." The paper is open access, and while the details of genetic measures and simulations can be hard to follow, I think it's a great example of the way recent work on selection and human diversity has been structured.

I'll just expand on a few of the topics in the paper, and discuss how they relate to the previous findings about the number and age of selected variants in human populations.

I have had a New York Review of Books essay by Richard Lewontin, titled, "Why Darwin?" on my desktop for a week without getting to the last section of it.

Like many essays in the NY Review of Books, Lewontin's shoehorns small points from the books into an argument of his own. As you might guess from the title, Lewontin's theme is that Darwin has been overrated -- a result of biologists overemphasizing a "great man" story of the history of their science, and an unjustified belief in the ubiquity and power of natural selection. Lewontin mobilizes his argument against Jerry Coyne's Why Evolution Is True.

I don't really find the "pluralist versus adaptationist" debate very interesting. Despite the vocal complaints of some, I can't ever seem to locate the mythical "adaptationists" who deny that non-adaptive evolution ever happens. So the "debate" always comes down to whether particular adaptive hypotheses are true. Since no scientific hypothesis is true a priori, and since "those adaptationists are always saying stupid things" is not a scientific argument, I don't see the point.

Still, I meant to get to the last section of Lewontin's essay, and this morning I finally read it. To close his case for the weakness of natural selection, Lewontin turns to another new book by Greg Gibson, titled, It Takes a Genome: How a Clash Between Our Genes and Modern Life Is Making Us Sick. The book is an extended account of "diseases of civilization", a topic that I discussed here last week ("Arrested adaptation and the 'diseases of civilization'"). Here's a passage from the book's promotional material (on the Amazon page):

In It Takes a Genome, Greg Gibson posits a revolutionary new hypothesis: Our genome is out of equilibrium, both with itself and its environment. Simply put, our genes aren’t coping well with modern culture. Our bodies were never designed to subsist on fat and sugary foods; our immune systems weren’t designed for today’s clean, bland environments; our minds weren’t designed to process hard-edged, artificial electronic inputs from dawn ‘til midnight. And that’s why so many of us suffer from chronic diseases that barely touched our ancestors.

Set aside for a moment how "revolutionary" this hypothesis is -- I'll revisit the idea in another post. The question is whether this mismatch between our environments and our genetic variation means that human evolution "stopped" or that we are still "adapted to the Pleistocene". As I pointed out in my earlier post, both propositions are true: human populations are mismatched with their current environments, and human populations have been recently adapting very rapidly to new environments. Here's what I wrote last week:

[M]any of today's chronic diseases reflect the reaction of human biology to novel environments for which our genes are not well adapted. But we don't need to exaggerate the slowness of human evolution to arrive at that conclusion. Recent rapid evolution of humans does not mean that humans are perfectly adapted to the present. Far from it -- if human populations have undergone rapid genetic changes into the past thousand years, it is a strong sign that fitness has not yet maximized in the post-agricultural environment.

I can contrast my point of view with Richard Lewontin's, who perfectly reiterates the "human evolution stopped in the Pleistocene" version of events.

An important property of adaptive evolution is that it is usually a slow process. Certainly there are cases where a single genetic change can mean the difference between life and death in a hostile environment. The classic cases are the mutations that give pathogenic microorganisms the ability to resist antibiotics or mutations that allow crops to resist pathogens, for example insects or herbicides. But these are not representative models for how species adapt, by accumulation of mutations of small effect, to changes in food availability, temperature modifications, and the thousand shocks that flesh is heir to. The usual small differences in fitness among genotypes are therefore manifest as detectable evolutionary change only after thousands of generations.

This deliberate tempo has presented the human species with a problem of adaptation. With a human generation of about twenty-five years, there have been roughly only one hundred generations since the founding of the Roman Republic. Yet the changes in the human environment caused by changes in human activity have been enormous. Changes in diet, habitation, working conditions, the pollution of air and water, and especially the considerable increase of lifespan that result in major alterations and breakdowns in the bodily machinery have all been too rapid for genetic adaptation.

Notice the false premises: Adaptive evolution is "usually a slow process." Species adapt by "accumulation of mutations of small effect." It's as if he were transported back in time to 1908 where no one had heard of the breeder's equation.

There's nothing impossible about long series of small changes. But they are not the only mode of adaptation, or even the most likely one. Populations with additive genetic variation that correlates with fitness will change rapidly under selection. The structure of the additive variation may lead to strong selection on one gene of large effect, or selection in parallel across many genes of varying effects. Series of small changes may be required for some adaptations, but a rapid environmental change (as Lewontin observes for humans) may cause bursts of rapid changes in allele frequencies.

To maintain the slowness of human evolution, Lewontin must do three things:

1. Assume humans are genetically uniform.

2. Where humans obviously are not uniform, argue that variations are uncorrelated with fitness.

3. Ignore any historical or genetic evidence that might contradict 1 and 2.

Keeping in mind the short length of this section of the essay, Lewontin does manage all three of these conditions.

I think it's downright sneaky the way Lewontin reinforces the assumption of human genetic uniformity. He refers to "the human genotype" as if there were only one! By emphasizing that "parts of the human genome are out of correspondence with modern life", he precludes the possibility that some human genomes may be more in correspondence than others. Sure, if humans share a single genome, they can't possibly differ in any adaptive way.

But diversity is the reality. Examples of recent human evolution are fixtures in biology textbooks, from sickle-cell to lactase persistence. These are traits that have rapidly changed in frequency during the last 2500 years, due to changes in recent human environments -- disease for the former, diet for the latter. These rapid transformations in precisely those that Lewontin says are impossible -- environmental changes being "too rapid for genetic adaptation." A number of morphological changes are also evident when comparing archaeological and recent skeletal samples in many parts of the world. Somehow the relevance of these recent changes goes unmentioned in the essay.

One of the best-characterized examples of evolution in recent populations is the rapid Holocene evolution of pigmentation phenotypes. It's a textbook example of human variation, and several adaptive hypotheses may explain it. So pigmentation would seem an unlikely example of how human evolution has been too slow to cope with the environment. But Lewontin finds a way:

[H]igh doses of solar radiation that is experienced by surfers on the California beaches might induce an eventually fatal skin cancer, but the cancer death almost always occurs well after reproductive age, so there is no opportunity for selection to act.

I agree that current patterns of cancer mortality of light-skinned surfers may have little impact on their fitness. In other words, this chronic disease is a sign of an environmental "mismatch" that future genetic evolution is unlikely to erase.

But why turn to false arguments about the speed of evolution to make this point? Surely Lewontin knows that "reproductive age" in humans is not synchronous with reproductive effort? Skin cancer is one of the earliest-killing cancers, with a good fraction of victims dying at ages when they might otherwise be helping raise their kids or grandchidlren. Lewontin must also know that human populations vary greatly in their skin cancer susceptibility, and that some surfers (the dark pigmented ones) have lower skin cancer rates after the same sun exposure. Skin cancer may or may not be the best explanation for dark pigmentation in low-latitude human populations (there are others, none mutually exclusive), but this example works strongly against Lewontin's claims that natural selection is "slow" and that human environmental changes have been "too rapid for genetic adaptation." We aren't perfectly adapted today, and the rate of our evolution in the recent past was very fast.

References:

Lewontin RC. 2009. Why Darwin? New York Review of Books 56(9) May 28, 2009. Online

While I was browsing papers for a research project, I happened to re-open the paper, "Stone Agers in the fast lane," written by S. Boyd Eaton, Melvin Konner, and Marjorie Shostak in 1988. This paper reviewed the idea that many chronic disorders like diabetes and cardiovascular disease are actually "diseases of civilization" -- brought on by a mismatch between the human genetic heritage and the current cultural milieu.

I'm citing this work as part of my continuing observations on biologists who predicted that human evolution must have stopped sometime in the Pleistocene. Eaton e-mailed me very soon after our acceleration paper was published, and it is only fair to say that the 2009 views of these authors may be very different from their 1988 publication. With that note, here's a quick review:

The current genetic variation in any species is a product of evolutionary forces that affected that species' ancestors in the past -- that's a basic precept of evolutionary theory. So it's hardly more than a syllogism that if the human environment has undergone recent rapid changes, then our genes may do little to protect us from undesirable biological side effects of our new environment.

But Eaton and colleagues, like many human biologists, went rather further than this observation. They made a point of emphasizing that the pace of human adaptation has been incredibly slow. The hypothesis of very slow human evolution had an desired corollary: the "diseases of civilization" are not merely bad side effects of recent dietary Westernization, but may ultimately be traced to the transition to agriculture -- an event that occurred 10,000 years ago in some societies. Let's consider how they emphasized this idea that human evolution had been glacially slow:

The gene pool from which modern humans derive their individual genotypes was formed during an evolutionary experience lasting over a billion years. The almost inconceivably protracted pace of genetic evolution is indicated by paleontologic findings that reveal that an average species of late cenozoic [sic] mammals persisted for more than a million years, by biomolecular evidence indicating that humans and chimpanzees now differ genetically by just 1.6 percent even though the hominid-pongid divergence occurred seven millino years ago, and by dentochronologic data showing that current Europeans are genetically more like their Cro-Magnon ancestors than they are like 20th-century Africans or Asians. Accordingly, it appears that the gene pool has changed little since anatomically modern humans, Homo sapiens sapiens, became widespread about 35,000 years ago and that, from a genetic standpoint, current humans are still late Paleolithic preagricultural hunter-gatherers (Eaton et al. 1988:740).

Not only was the pace of evolution slow when it was happening, but we may have reason to think that recently our gene pool hadn't been changing at all:

The Late Paleolithic era, from 35,000 to 20,000 B.P., may be considered the last time period during which the collective human gene pool interacted with bioenvironmental circumstances typical of those for which it had been originally selected (Eaton et al. 1988:740).

The word "originally" in this passage may admit of later changes in selection and thus in some genes. But the paper does not examine known cases of recent change, even on those genes where some kind of recent dietary adaptation was well-known in 1988 -- such as lactase persistence or ALDH2.

Reading the paper from my current vantage point, where do I think it went wrong? The basic point in the paper is undoubtedly correct -- many of today's chronic diseases reflect the reaction of human biology to novel environments for which our genes are not well adapted. But we don't need to exaggerate the slowness of human evolution to arrive at that conclusion. Recent rapid evolution of humans does not mean that humans are perfectly adapted to the present. Far from it -- if human populations have undergone rapid genetic changes into the past thousand years, it is a strong sign that fitness has not yet maximized in the post-agricultural environment.

Besides that, dietary influences on health may implicate the rapid cultural and ecological changes of the past 200 years. Westernization of diet is a characteristic of post-industrial economies, not early agriculturalists. Given the reduction in variance of mortality in the last 100 years as well as the short time, it is pretty likely that the genes of human populations have changed little in response to dietary Westernization.

I think that the rapidity of recent adaptive evolution does imply a different perspective on the "diseases of civilization." For one thing, some people may be resistant to these diseases because they have inherited new protective alleles. If humans had hardly evolved in the post-agricultural environment, we would expect all populations to be equally susceptible to type 2 diabetes, cardiovascular disease, and cancer. Instead, we find that different populations have different characteristic rates of these diseases after adoption of a Western diet.

Another insight is that some undesirable phenotypes may themselves be the consequences (or side effects) of recently selected alleles. Overdominant alleles like sickle cell naturally stand out in this regard. But the flushing reaction to alcohol, common in Asians with the selected ALDH2 allele, is a less fatal example.

References:

Eaton SB, Konner M, Shostak M. 1988. Stone Agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med 84:739-749.

After the last post, you might wonder what the big deal is about these information theoretic measures of linkage. After all, we’ve got lots of other measures of linkage to choose in population genetics, with many years of theory behind them. The basic conclusion about genetic drift was that it adds mutual information to samples over short regions, but that recombination over longer areas washes it out. If the net effect is no linkage, why would we bother to come up with some non-standard linkage measure?

One answer: If the existing linkage measures were so great for testing neutrality, then we might expect some of the recent genome-wide selection scans to have used them. But they didn’t – instead we have several partially incompatible methods, all of which eschew the usual measures of linkage.

Colin Renfrew is an archaeologist, in recent years well-known for his work on Neolithic Europeans and Indo-European origins. Last week, someone pointed me to his recent book, Prehistory: The Making of the Human Mind. I read a short review somewhere, but I've lost the link!

The book was first published in 2007, so its writing would have predated the publication of recent scans of the genome for selection. Renfrew of course has his own distinctive point of view, and he is not himself a geneticist. However, he has worked to integrate his work with genetic insights, interacts closely with many geneticists, and even coined the term, archaeogenetics, to describe a certain kind of gene-driven investigation of population history. So he's no neophyte when it comes to how geneticists describe the evolution of recent human populations.

A number of passages of the book are very interesting, from the perspective of the conventional wisdom about recent human evolution. I wanted to cite these paragraphs from page 92:

The genetic composition of living humans at birth (the human genotype) is closely similar from individual to individual today. That was an underlying assumption of the Human Genome Project and it is being further researched in studies of human genetic diversity. We are all truly born much the same. Moreover a child born today, in the twenty-first century of the Common Era, would be very little different in its DNA -- i.e., in the genotype, and hence in innate capacities -- from one born 60,000 years ago.

Then on page 93, after some additional discussion of Neandertal genetic results:

The implication here must be that the changes in human behaviour and life that have taken place since that time [between 60,000 and 100,000 years ago], and all the behavoural diversity that has emerged -- sedentism, cities, writing, warfare -- are not in any way determined by the very limited genetic changes which, as we understand the matter, distinguish us from our ancestors of 60,000 years ago. So the differences in human behaviour that we see now, when contrasted with the more limited range of behaviours then, are not to be explained by any inherent or emerging genetic differences. Modern molecular genetics suggests that, apart from the normal distribution range present in all populations in matters such as IQ, all humans are born equal.

This represents a widespread point of view, one with a long pedigree in archaeology and human genetics (refer also to my post on Ashley Montagu). Renfrew quite clearly claimed that human evolution stopped once humans became "modern". He emphasizes this point as the basis of a "paradox" -- the observation that no large anatomical changes correlate with the increase in archaeological complexity of the last 30,000 years.

I believe there is no paradox: rapid archaeological change certainly is no proof of evolutionary stasis!

I'm reading this interesting paper by Joseph Pickrell and colleagues, titled, "Signals of recent positive selection in a worldwide sample of human populations". The paper recounts the results of a selection scan in the Human Genome Diversity panel, which was reported in two publications last year. This is an interesting sample because it includes individuals from 53 population samples around the world.

I was waiting to present any observations about selection from the HGDP set until Pritchard's lab had published on them, since the initial publications had mentioned that this analysis was forthcoming. Now that it's appeared, I'll be pointing to a lot of these data in upcoming posts.

So I was reading with great interest. Then I found this statement:

Reports of ubiquitous strong (s = 1-5%) positive selection in the human genome (Hawks et al. 2007) may be considerably overstated (8).

I'm a little concerned that someone reading that might think that Pickrell and colleagues had actually tested our hypothesis about the number of recent strongly selected alleles. I'm also uncertain about the word, "ubiquitous", which means "everywhere." I mean, does that really sound like the kind of word I would use? It's just begging for trouble. It's like saying there's "ubiquitous" evidence of Neandertal contribution to the later European gene pool. Even if I thought it was true, I wouldn't put it in a paper!

We reported that roughly seven percent of genes appeared to be selected. Pickrell and colleagues list a rather large number of candidate loci for selection, and don't give any estimate or test of the number genome-wide. I think one might be able to count the regions listed in the data supplement for an estimate of what they thought was important enough to list, but I can't get the supplement yet. Since these candidate loci require 16 supplementary figures to list, maybe there are a lot of them. They do list a subset of more than 110 in the paper itself.

So what's the basis for saying we overstated anything? They suggest one reason for caution about the interpretation of candidate loci for selection:

We find that putatively selected haplotypes tend to be shared among geographically close populations. In principle, this could be due to issues of statistical power: broad geographical groupings share a demographic history and thus have similar power profiles. However, strongly selected loci are expected to show geographical patterns largely independent of demography—depending on the relevant selection pressures, they can be highly geographically restricted despite moderate levels of migration, or spread rapidly throughout a species even in the presence of little migration (Nagylaki 1975; Morjan and Rieseberg 2004) (8).

But wait a minute! If a gene were selected strongly and still polymorphic in human populations, it shouldn't be very old. So it can't have spread rapidly throughout the human species even in the presence of little migration. There hasn't been any time for this kind of spread.

To give a little mathematical perspective, one common way of modeling the dispersal of an advantageous gene is the Fisher diffusion wave model. In a Fisher wave, the gene grows logistically at any single point in space, and the allele frequencies form a standing wave that travels through space at a constant velocity. That velocity in a population uniform across 2-dimensional space is σ times the square root of s, where s is the selection coefficient and σ the root mean square dispersal distance -- basically, the average distance a person moves between his birth and the birth of his children.

If we want to know about dispersal of selected genes in early agriculturalists, we will need to know how far they move -- that's generally less than 10 km on average. So a gene selected strongly with a 5 percent advantage should move around 2.2 km/generation. Over the 400 generations since the beginning of agriculture, we'd expect a new allele to have dispersed across an area with a radius of less than 1000 km.

So in other words, it's just implausible that a selected allele would have a geographic distribution very different from drift, at least under the Fisher wave model. But obviously, some alleles have gone a lot farther than 1000 km in the last 10,000 years. Humans don't disperse strictly according to a Gaussian distribution, as assumed by the Fisher model; they sometimes disperse long distances. This can have a large impact on the spread of an advantageous allele. But it is an irregular phenomenon -- a stochastic event.

Let's consider the results a bit further. Here's a passage from page 1:

We find extensive sharing of putative selection signals between genetically similar populations, and limited sharing between genetically distant ones. In particular, Europe, the Middle East, and Central Asia show strikingly similar patterns of putative selection signals.

Which is exactly what we would predict from the history of these populations. Most signals of selection in Europe are Neolithic in date. The Neolithic was not only a time of massive population growth, but also the time of greatest mismatch between the human population and its novel agricultural environment. The dispersal of Neolithic lifeways from West Asia into Europe, and the recurrent incursions of Central Asian languages westward across the steppe into Europe and southward into the Indian subcontinent are the major features of the last 10,000 years of history in those regions. Don't we expect them to share a lot of selection? And if it took the massive migrations and interactions in those regions to generate this shared pattern of selection, shouldn't we expect other regions of the world, which lacked as extensive long-distance movements, to share fewer?

In this case, the critical information for evaluating the evidence is historical and archaeological. We can't just say that the candidate loci for selection have a similar geographic distribution to those that aren't selected. We need to evaluate the likelihood that they would have some other distribution. That likelihood is very low for most instances of selection, but may be high for a fraction of cases, or for some regions where long-distance dispersal was a more important aspect of population history.

So if we have a locus that is inconsistent with drift on the basis of linkage, we can reject drift. What if the geographic distribution is still consistent with drift? Should we doubt the linkage analysis? I don't see why -- basic biogeography says that most recently selected genes should have similar geographic distributions to drift.

References:

Pickrell JK, Coop G, Novembre J, Kudaravalli S, Li JZ, Absher D, Srinivasan BS, Barsh GS, Myers RM, Feldman MW, Pritchard JK. 2009. Signals of recent positive selection in a worldwide sample of human populations. Genome Res (early online) doi: 10.1101/gr.087577.108

My series on mutual information and tests of selection (which began with "Information theory: a short introduction") is at a branching point. One of the critical factors determining the power of such tests is the ancient rate of genetic drift. So it's important to come to some understanding of the archaeological record and our best estimates of ancient demography, so that we can independently test the hypothesis that genetic drift was very strong in recent human evolution. That's a long project, potentially the topic of several review papers. Since nobody else has put together these data in useful way for population genetics, I'm going to do it in one place. What you see in this series are my notes about this project. Being notes, they are not complete, but they may occasionally be better than any other sources. Where it's appropriate, I'll spin off the results for review and publication, and point to them here.

Many geneticists believe that there were massive population bottlenecks within the last 30,000 years, citing both genetic and archaeological evidence in support of this proposition. Some claim that there have been significant population bottlenecks in the last 5000 years.

Some archaeologists agree. However, I think this is one of those Inigo Montoya cases: "That word, I do not think it means what you think it means." Archaeology and genetics have completely different interpretations of the words, "bottleneck," "contraction," and "expansion." The result has been a lot of confusion about the relation of archaeological and genetic estimates of population size.

A population bottleneck impacts genetics by increasing the rate of inbreeding. This takes time to change gene frequencies, and does so in inverse proportion to population size. It may seem surprising that a truly massive die-off, on the scale of the Black Death, will have no measurable genetic impact. But cutting a population of millions down by half just doesn't impact gene frequencies. That is, unless you are looking at genes that helped people to survive the plague, in which case you're looking at natural selection, not a bottleneck.

A significant genetic bottleneck is not just any population contraction -- it's an event in which the population is cut by a large fraction for a long time. In paleontological terms, we're usually considering cases where the ratio of the number of individuals and the number of generations is near one. In other words, if you cut the population down to a thousand individuals, and keep it there for a thousand generations, you're going to have a large genetic impact. Likewise, you can have a significant bottleneck that's ten generations long, but you need to cut the population down to around ten people.

You can do a bit better measuring inbreeding by looking at lots and lots of people to study very rare alleles, like a rare genetic disease in a founder population. There, you may spot changes that unfolded in ten generations, even in a relatively large population of a hundred people. Increasingly, as we develop larger and larger datasets of gene variations, we will add power to detect such events in human prehistory.

In archaeology, a significant event is one in which fewer sites were occupied by ancient people in a well-studied region. The length of such a contraction depends on the sampling intensity and dating methods available -- it might be a hundred years or many thousands. Likewise, the magnitude of population contraction will be uncertain -- you can get an accurate estimate, but with substantial sampling error. As in genetics, there are other possible explanations for an apparent contraction. We might lack geological exposures of the right age, or people may simply have moved from formerly favored locations to new ones. Worse, it might just be that archaeologists haven't looked hard enough at a given time interval.

Archaeology is necessarily imprecise about the census population that existed at any given time. So is genetics. Both have their strengths and weaknesses. We want these different areas of evidence to bear on the same prehistoric events.

Too much, instead of testing hypotheses, people just line up chronologies and look for matches. A geologist may claim that African paleoclimate is important because it may explain ``modern human origins.'' An archaeologist may claim that a hiatus at a site is consistent with ``genetic bottlenecks.'' And the geneticist may claim that inbreeding in a modern-day genetic sample dates to a period of time corresponding to the replacement of one tool industry by another.

Any might be a valid hypothesis, but we need to take it further, to actually provide some tests. I believe we can do better now, because of the growing amount of genetic information. But we're going to have to do away with the facile idea that we're looking for massive bottlenecks, we need to introduce a recognition of the role of selection in human genetic variation, and we need to start addressing the archaeological record as it really exists.

That's a forward to what follows. I'm going through regions of the world at different time intervals, to discuss what we know about population size from the archaeological record.

Next: No Late Pleistocene bottleneck in southern Africa

We tend to think of genetic drift as a random process. Random processes operating repeatedly over time are called “stochastic,” and changes in gene frequency under genetic drift are certainly that.

Since entropy is a measure of uncertainty, it might seem natural to think that stochastic changes in gene frequency would increase the entropy in a population. After all, the gene frequency in a population under genetic drift will be more and more uncertain over time. So, considering the frequency of a single allele as the system, genetic drift appears to increase entropy over time.

But even this simple system isn’t quite so simple as it might appear. Sure if you start out knowing the allele frequency, then genetic drift will increase your uncertainty over time. You will become less and less able to say that it lies in any given interval. But what if you don’t start out knowing? What if all you know is that the locus has been subjected to t generations of genetic drift?

As t increases, the probability of fixation of the locus also increases. The net effect is to reduce the entropy in the system – going from uncertainty about the allele frequency to more and more certainty that it will be either one or zero. The only thing that will stop this process is some other evolutionary force – mutation, migration from other populations, balancing selection. Each of these will have its own distinctive effects on the entropy of the single-locus system.

Brian McEvoy and colleagues report in Genome Research that recent natural selection accounts for many of the largest differences between today's English, Irish, Dutch, and Scandinavian populations:

Geographical structure and differential natural selection amongst
North European populations

...There is evidence from F_ST based analysis of genic and non-genic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic [sic]...

Two things. First, I have to write a paper with the word "amongst" in the title!

Second, if we look closer in the paper, we find that the evidence for selection is more diffuse -- not limited to the "Immunity and Defense" category -- but that category is the only one with a disproportionate increase. The rationale for natural selection is that the high-F_ST SNPs between their samples are disproportionately in genes. If these differences were neutral, the high-F_ST SNPs would be equally non-genic.

In fact, there should be a slight deficit of genic SNPs, since these are constrained by purifying selection. This is a good argument against a couple of papers that appeared last year, that suggested Europeans had undergone intense bottlenecks leading to a disproportionate number of deleterious SNPs. If that were actually true, the genic SNPs would not look different from the non-genic SNPs, or if anything purifying selection in the last few thousand years would have made them more similar, not more different.

OK, so genome-wide, the high-F_ST SNPs are more likely to be genic. Then, they compared all functional classes to see if selection was concentrated in any particular categories:

The ‘Immunity and Defense’ (BP00148) category is the only one of the 23 ontological terms (with sufficient numbers to be tested) to show a significant enrichment of high F_ST SNPs after correction for multiple testing (p=0.0012, Adjusted Significance Level = 0.0022).

which itself is pretty surprising -- it took a lot of hits on many SNPs to make that signal. This comparison is really only going to pick up SNPs that are very tightly linked to a selected variant, and won't pick them up if the history of the many populations has been too similar -- that's why lactase doesn't show up, for example.

Anyway, the paper discusses several other genes that are not immune-related with high differentiation among these Northern European samples, and they give a list of some rather long regions that appear to have been selected, where they cannot identify the selected locus.

I think a more powerful test could be applied to these data. The F_ST analysis is the first step, using geography as a test of differential change over space. But we can probably do better than this with a test that actually considers the dispersal pattern of selected genes, in comparison with the population history. That will take some involved demographic modeling, but selected genes ought to really stand out.

References:

McEvoy BP and 26 others. 2009. Geographical structure and differential natural selection amongst North European populations. Genome Res (early online) doi: 10.1101/gr.083394.108

A reader helpfully pointed me to a new paper in PNAS that looks at the sampling scheme of the 1000 Genomes Project from the point of view of SNP discovery. They frame the question as "How many variants are yet to be found?"

Here's part of the abstract:

Consistent with previous descriptions, our results show that the African population is the most diverse in terms of the number of variants expected to exist, the Asian populations the least diverse, with the European population in-between. In addition, our results show a clear distinction between the Chinese and the Japanese populations, with the Japanese population being the less diverse. To find all common variants (frequency at least 1%) the number of individuals that need to be sequenced is small (∼350) and does not differ much among the different populations; our data show that, subject to sequence accuracy, the 1000 Genomes Project is likely to find most of these common variants and a high proportion of the rarer ones (frequency between 0.1 and 1%). The data reveal a rule of diminishing returns: a small number of individuals (∼150) is sufficient to identify 80% of variants with a frequency of at least 0.1%, while a much larger number (>3,000 individuals) is necessary to find all of those variants.

Well, if the main goal of the 1000 Genomes project is better chip design for the future, then this question -- what fraction of rare variants will be ascertained in the sample -- is the most pertinent.

However, I for one am looking forward to the larger sample for a different reason. It should allow us to test for recent selection on lower-frequency variants. It may also help to localize the sites under selection. For that, I'm not all that interested in finding the one-percent alleles, I'm more interested in having a sufficient number of copies of them to test hypotheses about change over time.

At the end of the abstract, there is this interesting sentence:

Finally, our results also show a much higher diversity in environmental response genes compared with the average genome, especially in African populations.

I can't get the PDF today, so I'll be waiting to find out what this actually means. That is, I have no idea what they mean by "environmental response" genes.

References:

Ionita-Laza I, Lange C, Laird NM. 2009. Estimating the number of unseen variants in the human genome. Proc Nat Acad Sci (early online) doi:10.1073/pnas.0807815106

Larry Moran has been writing a series of posts about quality science journalism. These have included descriptions of some well-written journalistic accounts of evolutionary science, and other that are in his opinion not so well-written.

In this latter category -- what Moran considers to be poor examples of journalism -- he puts a recent article about my work, by writer Kathleen McAuliffe, which appeared in the March 2009 issue of Discover.

Naturally I disagree. After speaking with McAuliffe several times and showing her around my lab here in Madison, I believe she has done an excellent job of describing our research, as well as putting it in the context of recent studies of human variation and evolution.

I think that Moran's criticism can be split into three points:

1. The article opposes our work against the straw-man view that "human evolution stopped."

2. The article does not spend enough space describing the views of scientists who doubt that human evolution accelerated, or who doubt the amount of acceleration.

3. The article includes some speculative "just so stories" for the causes of selection on some genes.

Those three points are too many for a single blog post, so I will focus on the first.

This isn't a long essay; just a pointer to a Nature feature by Erika Check Hayden where I make an appearance to represent the anthropological viewpoint on recent genetic changes:

[C]urrent human populations are much more genetically diverse than this hypothesis predicts, so Moyzis and Hawks have concluded that evolution must have ramped up over the past 40,000 years. They chalk some of this acceleration up to human population growth, which exposed the species to more new mutations and created more raw material for selection. But the other reason, Hawks thinks, is culture — because although the physiology of humans has not changed much in the past 40,000 years, their expansion and migration means that lifestyles, languages and technologies certainly have.

Although not everyone agrees with Hawks's claims, the best understood example of recent human evolution does seem to fit. Genetic mutations that allow adults to digest lactose, a sugar found in milk, have emerged independently in different populations in response to the same cultural innovation — cattle domestication. "I don't see culture as an alternative to genetics, I see culture as being the explanatory factor for these genetic changes," says Hawks. "There is no explanation for change without the gene–environment interaction."

Well, there's my Michigan training.

Others have sometimes had the view that culture should replace genetic change in recent human history. I think that's wrong. Culture constrains genetic changes. Some kinds of cultural evolution can fall into relatively stable patterns that allow longer-term genetic changes to happen -- like the sustained subsistence changes brought on by agriculture. Those are great targets for adaptive genetic changes, and they might even generate circumstances that enable further cultural changes. That's a true biocultural evolutionary feedback.

Other cultural systems continue to fluctuate more rapidly. But this is nothing new -- many environmental changes fluctuate on a time scale too rapid for genetic changes to catch up. Even so, sometimes genetic polymorphisms occur as equilibrium solutions to such rapidly fluctuating systems. In any event, we can address these questions quantitatively.

The article contains a mix of stuff about human behavioral evolution -- ranging from recurrently selected genes in hominids up to our stuff on very recent evolution. Oh, and there's this:

Preuss says that such precise dissections of human-specific traits are still quite rare. "If you go beyond the bland expression of 'advanced cognition' and try to talk about cognitive mechanisms and abilities, we don't really know that much," he says. This means that there is a glut of genomic data but a paucity of crucial information from other fields that would help to make sense of it. "We need to start connecting this genetic world to the traditional anthropological approaches," agrees Hawks, who sees genomics as an inspiration to start collecting and sharing data on an equivalent scale in his own discipline.

That's a point I've made several times here, and I'm glad to see it coming out in my interviews elsewhere. We know so much now about the human genome, but we know yet more about the archaeological, linguistic and biological record of the last 20,000 years. It's not so easy to get all these data together. But there's huge potential here.

References:

Hayden EC. 2009. Darwin 200: The other strand. Nature 457:776-779. doi:10.1038/457776a

I want to point people interested in recent human evolution to a new book, The 10,000 Year Explosion: How Civilization Accelerated Human Evolution.

The authors, Gregory Cochran and Henry Harpending, are good friends of mine, and I have worked with them on some of the material covered in their book. So, you can hardly expect me to give an unbiased review!

However, I have now heard from a number of people not connected to the authors, who have read the book and enjoyed it. So it's not just me.

T. J. Kelleher reviewed the book in SEED, bringing out several interesting points:

Cochran and Harpending also find value in such work [as the Genographic Project], but they argue for a fuller appreciation of the geographic distributions of genes, and in doing so, they herald a new era not only in biological anthropology, but also for history. They do not stop with what information about human history can be found in the genes, precisely because many gene variants are not neutral. Where the usual geographical analysis treats the distribution of genes as an effect of history, in Cochran and Harpending's view, the genes themselves are a cause: Two variants in the same gene do not necessarily have the same effect, and the relative selective advantages and disadvantages of them will — not surprisingly, to anyone versed in evolutionary biology — influence the movements of genes through populations over both space and time.

That's a very ambitious agenda. On the way there, the book covers several topics of great interest to me. Naturally recent evolution by natural selection, particularly in post-agricultural populations, comes to the fore. The possible introgression of genes from Neandertals, as another source of possible adaptive variation in recent human evolution, also gets a chapter.

With this background in place, Cochran and Harpending explore some hypotheses that may link the distinctive histories of human groups to recent genetic changes and exchanges. One is the expansion and dispersal of Indo-European languages, a series of events that anthropologists have tried to connect to a jumble of different factors, ranging from conquering hordes of steppe nomads to conquering hordes of Anatolian farmers. Cochran and Harpending suggest that pastoralism and the resulting population growth connected to milk consumption was the prime mover.

Another hypothesis connects the psychometric literature on Ashkenazi Jewish people to some of the distinctive genetic disorders common in that population, such as Tay-Sachs disease, Gaucher disease, torsion dystonia and others. In a nutshell, Cochran and Harpending suggest that natural selection for general intelligence has occurred during Ashkenazi history, resulting in a distribution of IQ between 0.5 and 1 standard deviation above the European mean.

I can just imagine many readers twisting in their chairs when reading this chapter. And they should: relying upon both documentary evidence and whole-genome surveys of variation Cochran and Harpending puncture several myths about Jewish history, psychometrics, and admixture of populations. In the past, human geneticists have been all-too-willing to believe completely bogus scenarios of population history. The idea that Ashkenazim underwent a severe and prolonged population bottleneck, completely isolated from the surrounding European population, is one of the most pernicious of these scenarios. Cochran and Harpending's hypothesis, that alleles causing sphingolipid storage disorders were positively selected in Ashkenazi populations of the last 1500 years, is plausible and certainly testable. Plausibly, these alleles may have been selected for their roles in some other function, although none suggest themselves. The bottleneck theory, on the other hand, is not plausible, refuted by both the historical record and the genomic variation of living people of Ashkenazi descent.

I found the book to have a good combination of humor, interesting anecdotes, and description of new science. I've read most of the recent popular books about human evolution or genetics. To me, this one stands above the others. Maybe that's because I'm already thinking hard about the central proposition -- indeed the subtitle -- that "civilization accelerated human evolution." Like I said, I'm hardly unbiased.

But I think it's mostly more fun than most other genetics books. Some science writers cover their tentative approach to genetics by using dark, brooding prose. This book doesn't suffer from ponderosity, and its organization helps -- divided into dozens of little stories with odd historical facts, it's the kind of book you can stash in your bag for bus rides.

UPDATE (2009-02-19): I wanted to mention that Cochran gave a wide-ranging interview about the book to 2blowhards.

I had fun reading the interview because Cochran's suffer-no-fools attitude toward purely speculative ideas about recent evolution. He's looking for testable ideas, not mere generalizations. My favorite quote, with reference to an idea about behavior and mythological characters:

I think this line of analysis is about as sound and solid as Citibank.

Harpending also makes an appearance worth quoting, referring to the question of how much of the book is scientifically established and how much is speculative:

The basics are secure -- population genetics, demography, history, etc. But there are certainly a number of hypotheses we have that are not solidly established. But that is the way science works. If something were rock solid it would be widely known and would be too boring to talk about in the book. We don't spend a whole lot of time for example on malaria defense polymorphisms.

We really hope to see our hypotheses tested, maybe modified, maybe falsified, or not. We don't believe them in any strong sense. Whenever you read a scientist who is deeply committed to his or her ideas, hang on to your wallet!

Our work on recent selection was featured in Discover magazine this month. I'll link to that later. In the meantime, I've been getting some thoughtful letters from readers of the article. I thought I would post some of these letters with answers, because they really illustrate a cross-section of interest in the work. Here's the first:

I am just a private citizen, but I have thought about something for some time. Let's take 1,000 sets of identical twins and divide them into two groups. The groups will be put far apart and never come in contact with each for 1000 years. The two areas the two groups go to are identical and the number of them stays at 1,000.

After the 1000 years they are brought back together. I will wager $10,000 the two groups will have evolved differently, even though they lived in identical climates. Is anyone willing to take me up on the bet?

I am guessing if we took one set of identical twins who could live for 1000 years, separate them for the 1000 years in identical climates, the same thing would happen.

My thinking is that climate is part of the evolution process, but the more complicated life gets means the body has to adjust to the changes. If one group's environment doesn't change, then they only have to adjust to the environment once. If the other group starts to invent things and are constantly improving on things, then they have to keep evolving to the constant changes. I say living in one area that keeps changing for 1,000 years will change the person.

There's a bit more to this letter, which I may include later. In the meantime, here's what I wrote in response:

Thank you for your letter. In fact you are entirely correct; if you separate two sets of identical people for 1000 years, the two populations will evolve differently. This will be much more so if you separate 100 people instead of 1000, as the chance element of evolution is the largest factor in these small populations.

Now, on the other hand, if you separate two groups of 100,000 or 1,000,000 people for 1000 years, we will see very little genetic change at all in either group. Except to the extent that their genes are subject to selection.

But as you mention, the genes of these large populations may evolve differently even if their phenotypes are subject to the same environment. For example, Europeans and north Asians have both evolved lighter skin color in the last 20,000 years. But in these two populations we see very different genetic changes. Europeans have a high frequency of new genetic changes in genes like SLC24A5, OCA2, and Mc1r; Asians also have a change in Mc1r but lack the others; instead they have changes in other genes like DCT.

Again and again in recent human evolution, we see that chance element influencing the variation that selection has to work with. In maybe the most famous example, different populations have come to suffer from falciparum malaria in the last 5000 years. In these populations, we see diverse mutations that help to resist the malaria parasite. The sickle cell trait became common in West Africa and north India; West Africa also got hemoglobin C and G6PD deficiency. Hemoglobin E arose in southeast Asia; alpha- and beta-thalassemia appeared in the eastern Mediterranean and elsewhere; ovalocytosis in New Guinea. These different genetic adaptations have different values and different costs. If humans had always lived in a single population exposed to malaria, some of these adaptations may not have proliferated. But the long distances and slow movement between these populations means that new adaptations can grow in numbers faster than they spread to different parts of the globe.

I certainly wouldn't take up his wager. But who knows, there may be a profit opportunity here -- there are a lot of folks studying human genetics who don't think evolution in recent humans is possible!