Human evolution has accelerated
The embargo has now ended on the second, and far more important paper that I mentioned the other day. It is a product of work I've been doing with Bob Moyzis of UC Irvine, his former graduate student Eric Wang, now at Affymetrix, my friend Greg Cochran and Henry Harpending at the University of Utah.
Some readers may know I've been working on this project -- I've given presentations at meetings and at a number of universities about it. But otherwise I've been silent about it. In particular I have been systematically avoiding the topic of recent selection here on the weblog. It has been a great inconvenience to me, but the unhappy fact is that journals want new results, and blogging about something is at least perceived to reduce its news value. And of course, working with other people across the country entails a lot of respect for keeping discussions and results confidential until we have all signed off on everything.
Anyway, I'm hugely excited about this project, our current results, and what we will be doing next. Which means I have some pent-up writing to do! Over the next few days, this will be acceleration central -- I'll be laying out what these genomic data mean for recent human evolution, what kinds of genes we have been finding under selection, and exactly how these kinds of analyses are done.
I'll also be tracking press articles and blog reactions to the paper. PNAS is, if anything, consistently unpredictable about when they actually make papers available. If you want a preprint, please let me know. I'd also appreciate your links.
Also, if you've come here for the first time, welcome! I may get a lot of traffic for a few days, so I apologize if things are slow.
Here's a start: the abstract.
Recent acceleration of human adaptive evolution
John Hawks, Eric T. Wang, Gregory Cochran, Henry C. Harpending, and Robert K. Moyzis
Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during the last 40,000 years. We tested the null hypothesis that the observed age distribution of recent positively selected linkage blocks is consistent with a constant rate of adaptive substitution during human evolution. We show that a constant rate high enough to explain the number of recently selected variants would predict (i) site heterozygosity at least 10-fold lower than is observed in humans, (ii) a strong relationship of heterozygosity and local recombination rate, which is not observed in humans, (iii) an implausibly high number of adaptive substitutions between humans and chimpanzees, and (iv) nearly 100 times the observed number of high-frequency linkage disequilibrium blocks. Larger populations generate more new selected mutations, and we show the consistency of the observed data with the historical pattern of human population growth. We consider human demographic growth to be linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of our species.
This is a bold assertion, and I will be putting out an FAQ later today that covers many of the questions I have been fielding from the press. There is a lot of technical detail in it, but we have accomplished essentially two things:
1. An empirical age distribution for alleles under recent selection, which number in the thousands.
2. A theoretical account of why these new alleles should have been increasing rapidly in numbers during the last 40,000 years.
It is a powerful paper because it shows why a rapid acceleration of our evolution is expected in theory, and it matches those expectations to real empirical data. It shows the absolute impossibility of a constant rate of selective change in humans, and that gives reality to our estimate of the amount of acceleration.
The last paragraph of the discussion:
It is sometimes claimed that the pace of human evolution should have slowed as cultural adaptation supplanted genetic adaptation. The high empirical number of recent adaptive variants would seem sufficient to refute this claim. It is important to note that the peak ages of new selected variants in our data do not reflect the highest intensity of selection, but merely our ability to detect selection. Due to the recent acceleration, many more new adaptive mutations should exist than have yet been ascertained, occurring at a faster and faster rate during historic times. Adaptive alleles with frequencies under 22% should then greatly outnumber those at higher frequencies. To the extent that new adaptive alleles continued to reflect demographic growth, the Neolithic and later periods would have experienced a rate of adaptive evolution more than 100 times higher than characterized most of human evolution. Cultural changes have reduced mortality rates, but variance in reproduction has continued to fuel genetic change. In our view, the rapid cultural evolution during the Late Pleistocene created vastly more opportunities for further genetic change, not fewer, as new avenues emerged for communication, social interactions, and creativity.
Over the next few days, I'll fill you in a bit about the course of this research -- how we got started, how it proceeded, and what parts of it remain exciting. Also, I'll try to give a flavor to what genomics means for anthropology -- what exactly is "anthropological genomics?" I think that there is an exciting frontier opening in the way we look at the past, and I hope to be able to show how some of it will work over the next few years.
Evolution of the monkeyflowers
Spring has finally come to us here in the North, and it's time to start thinking about planting. So, when I went to a seminar yesterday by John Willis, it was with dual motives.
Naturally, I was interested in hearing about his work relating the evolutionary ecology of Mimulus species to their genomics. As Willis and his many former and current lab members made clear in a recent review article in Heredity, monkeyflowers have become a really interesting model system for studying the dynamics of natural selection on genomes -- particularly, with relation to local ecological adaptation, and also with relation to speciation.
But I was also thinking about whether I could find a nice flower variety for my garden. I'm not particularly excited about peas, and I tolerate Arabidopsis when it comes up, but let's face it, it's not exactly a show flower. I'd love to get one of the prettier hawkweeds going (these have eponymical appeal as well as botanical interest) but the common ones are pretty boring.
Well, Willis's lab has been a center of development for Mimulus genetics. They have developed a store of SNPs and other markers (available at the Mimulus evolution website) for QTL mapping, and are using them to find genes responsible for ecological adaptations in different wild Mimulus populations. In the talk, Willis featured some of his collaborators' work finding genes involved in wet versus dry habitat adaptations and in early versus late flowering. These traits are connected to each other, as well as to other life history, plant size and flower size.
I left having my prior belief abundantly confirmed: botany is awesome. I mean, think about it. You can go outside, in your own neighborhood, and study biology. You can uproot your subjects and transplant them somewhere else, to watch how well they do. If they die, well, that's a data point, not an ethical emergency! Worried about gene-environment interactions? No problem, just put samples of all your subjects in the same greenhouse and wait. Need to isolate a QTL against a uniform genetic background? Cool, just repeatedly backcross it into an inbred line for a few generations, selecting for the trait each time. Want to study genetic correlations? Well, you can breed a thousand plants and select for any trait you want!
Oh, and if you want to, you can clone them.
Let's look at an example, from the Heredity review:
Recent work on floral evolution demonstrates that fundamental evolutionary questions can be addressed in Mimulus through the combination of field experiments and modern genomic approaches. Bradshaw et al. (1995, 1998) pioneered the application of genome mapping to study of ecologically important traits in Mimulus using RAPD and allozyme markers to map floral QTLs underlying the divergence between red-flowered, hummingbird-pollinated M. cardinalis and pink-flowered, bee-pollinated M. lewisii. The initial mapping experiments, with hybrid phenotypes measured in controlled greenhouse environments, revealed QTLs with major effects on virtually every floral character studied, from coloration and morphology to nectar production. To determine the effect of these QTLs on pollinator visitation and discrimination, Schemske and Bradshaw (1999) moved the genotyped hybrids to a field site near one of the few regions where the species coexist, and observed bee and hummingbird visitation behavior. Amazingly, the M. cardinalis allele at a single QTL, YELLOW UPPER (YUP), was responsible for an 80% loss of visitation by bee pollinators, and the M. cardinalis allele at a QTL responsible for variation in nectar production doubled hummingbird visitation (Schemske and Bradshaw, 1999). Bradshaw and Schemske (2003) subsequently created near-isogenic lines (NILs), where heterospecific alleles at YUP were reciprocally introgressed into the parental genetic backgrounds, and evaluated the response of pollinators to the NILs in the field. They observed an even clearer pattern of pollinator discrimination due to this locus, with a 74-fold increase in bee visitation in M. cardinalis NILs that carried the M. lewisii YUP allele, and a 68-fold increase in hummingbird visitation in M. lewisii NILs with the M. cardinalis YUP allele. Although the ecological context, in this case the community of potential pollinators, is certainly important to the evolution of new pollinator associations, these results also demonstrate that single genomic regions can have a large effect on major evolutionary transitions (Wu et al. 2008: 224-225).
The talk was mostly focused on the Mimulus guttatus complex, where some of the most pressing issues are life history, drought tolerance, and tolerance of high mineral concentrations, such as salt or copper. They were able to trace many QTL's of small effect with relation to the major differences in life history and moisture requirements in ecogeographic races of M. guttatus, to show that the within-population variation for these traits is caused by high-frequency (likely balanced) alleles rather than mutation-selection balance or rare alleles, and to find the correlated responses to selection of different plant traits based on different QTL's.
With respect to the genetics of speciation and ecogeographic race formation, they are helped by a long history of research on Mimulus. For example:
Macnair and Christie (1983) performed the first direct genetic analysis of hybrid incompatibilities in Mimulus. While studying the genetic basis of copper tolerance in California populations of M. guttatus, they noticed that some crosses between plants from the copper mines and certain other populations resulted in F1s that died as young seedlings. Further crossing studies revealed that the F1 lethality was caused by a deleterious epistatic interaction between the copper tolerance allele from the mine populations (or a gene tightly linked to it) and alleles at an unknown number of different loci from the other populations. Such deleterious interlocus interactions, usually referred to as DobzhanskyâMuller (D-M) incompatibilities, are thought to be the major cause of low hybrid fitness in plants and animals (reviewed in Coyne and Orr, 2004). Remarkably, it appeared that natural selection for copper tolerance had indirectly resulted in the evolutionary origin of the hybrid incompatibility (Wu et al. 2008:226).
So yes, say what you want, botany is awesome. Plus, there's one more thing: I sat through an entire lecture about natural selection and ecological differentiation of species and races, and never once heard the word, "bottleneck." It was like traveling to some kind of bizarro world where biologists still read Darwin!
So we come down to the really difficult question: which variety am I going to plant? Mimulus glabratus is native here in Wisconsin, including Dane County, but it is not very showy, and prefers wet habitat. That makes it a poor fit for my native plant patch, which is dry/mesic, and which I never water unless the black-eyed Susans and bee balms start to wilt. Mimulus ringens is prettier, with bigger, lavender flowers, but also likes it wet.
I guess I'll have to keep looking. M. lewisii is a pretty variant, if I can find a good source for it, and I can keep it in one of the wetter corners of the yard. I would try for M. cardinalis, since we have hummingbirds sometimes, but I'd like to get Lobelia cardinalis going also, and it's a lot easier to find. Besides, it hardly looks like a monkey!
References:
Wu CA, Lowry DB, Cooley AM, Wright KM, Lee YW, Willis JH. 2008. Mimulus is an emerging model system for the integration of ecological and genomic studies. Heredity 100:220-230. doi:10.1038/sj.hdy.6801018
Natural selection 101. Episode 1: The miracle of compound interest
--Originally posted August 24, 2007.
Once upon a time, somebody probably told you that biologists don't need to know any calculus. Well, I suppose they were right: it is certainly true that most biologists don't use any calculus in their work. A purely practical biologist is like a purely practical banker -- as long as the computers do their jobs, why does anybody need to know how to calculate?
Still, there is some point to knowing the theory that underpins the study of life. Math gives the theory its power. Understand the math, and you can unleash that power to find answers to new problems.
During the last year or so, I have written nothing here about natural selection, quite purposively, even though anyone who knows me at all can tell you I hardly talk about anything else. Well, I tend not to write about what I'm working on; especially when it involves other people's observations as well as my own. I don't like it that way, but sometimes it's necessary. It especially stings when the major news in biology is that the world has changed to make selection relevant again. Still, to do my part in this change, I've maintained a respectable silence.
Over this time, I have learned many mysteries about Darwin's force. Most geneticists approach natural selection as a kind of black magic. You see, find the right pattern of selection, and you can explain almost anything. You might think this is a desirable quality in a scientific hypothesis, but many people don't see it that way. Selection, in their view, is too often unfalsifiable. It's too hard to disprove. And besides, some things really do happen by chance alone. We have to give random chance at least a fair shot as an explanation, and if you can't disprove genetic drift (so the story goes), then you don't need to invoke selection.
Besides, genetic drift is a much happier, friendlier hypothesis than selection. If somebody dies by genetic drift, it's nobody's fault. "Ooops, just a spot of bad luck, there! Move along, nothing to see here." By contrast, selection thuggishly entails that deaths and births have causes. For some reason, the idea that something should have a cause is offensive to some biologists. That is, after all, the point of The Spandrels of San Marco: Adaptationism, the assumption that phenotypic "traits" have discrete (and identifiable) causes, is a metaphysical assumption, not a tenet of Darwinism. Even those biologists who don't conform to the philosophy of narrow adaptationism, as described by Gould and Lewontin, have often felt the sting of the word; a real scarlet "A" for their dossiers.
Perhaps more to the point, you can learn the essentials about genetic drift with a bit of algebra. Drift in a constant population is a linear process, and drift in non-constant populations can generally be approximated by linear modifications to the case of constant size. In contrast, natural selection is a logistic process, and understanding it requires differential equations.
A combination of philosophy and calculus. You can see how selection got its reputation as black magic.
Treat selection equally
Massimo Pigliucci gives a combative review of Michael Lynch's new book, The Origins of Genome Architecture. A short passage lauding the books first 12 chapters says that you should buy the book:
But before we get to the controversy, let me say that the book's first 12 chapters are a mustread for anyone interested in the evolution of genomes. This Origins represents a serious, valiant, and highly scholarly attempt at making sense of the new data provided by the genomic revolution. To that aim, Lynch deploys the full array of conceptual tools that make up the modern synthesis paradigm in evolutionary biology.
And then Piglucci engages with Lynch's final chapter, in which Lynch advocates a path for future research in evolutionary biology. Lynch built a long record of accomplishments in population dynamics, ecology, and conservation biology before he turned to genomics in the past decade. He is probably best known for emphasizing the importance of demographic constraints on genome evolution and variability -- for instance, the constraint on the strength of selection against weakly deleterious variants in vertebrates compared to vastly huger microbial populations. Pigliucci reads him as advocating a strongly transmission-centric view of genome evolution:
Lynch's thesis, as mentioned above, is that the theoretical apparatus of evolutionary theory is complete and that people should stop whining about missing pieces and the need for a new synthesis: just study your population genetics and everything will be all right.
This is, of course, a perfectly respectable opinion--although the repeated, if oblique, parallels Lynch draws between legitimate scientific opponents of his view and creationists who advocate intelligent design become increasingly irritating by the end of the chapter. Lynch, however, seems convinced that all that evolutionary theory has to explain is changes in allelic frequencies within populations. If that were indeed the case, the job is done, and we are now left with simply systematizing the huge amounts of information coming forth from genomic studies. As Carroll complains [in (8), quoted by Lynch], this is a rather uninspiring theme.
I like the clarity of casting this as a disagreement between Lynch -- advocating a view of evolution dominated by transmission genetics -- and Carroll, advocating a view dominated by form. But in the end it comes back to the old "bean-bag genetics" complaint, that studying the change in gene frequencies cannot itself test hypotheses about the distribution of morphological and developmental patterns
Tracking back to acceleranistas
I've had a very busy couple of days, and haven't been maintaining my reading-and-linking as much as I had hoped. So I wanted to take a few minutes to do a quick tour of the blogosphere to see what people are saying about the idea of acceleration.
I'm linking to posts I have read, and in some cases commented on. They are a mix of explanation of the concepts, applauding the ideas and analysis, and criticism of the methods. What I most want to point out is that the discussion on blogs is at a very high level -- people are reading the paper with much more precision than I have ever experienced in the peer review process. This is really the best that today's science community has to offer.
One of the best posts is over at LiveJournal, where shoshin works through the theoretical part of the paper. Naturally, this is my favorite part -- and shoshin describes things exceptionally well. The beginning is great:
The case for a recent acceleration of human evolution in the last 40K years (and especially the last 10K) follows pretty straightforwardly from evolutionary first principles combined with elementary facts about human history since the late Pleistocene. So straightforwardly, in fact, that you have to wonder why nobody thought of it sooner. It's one of those rare cases where the theoretical argument is so strong that you can pretty much use accordance with it as a test of experimental methods at least as much as the other way around.
Razib works through the paper at Gene Expression, in a long, detailed post. I like this part:
We are now the most numerous large mammal on the face of this planet. Using the data above the authors imply that our species has been subject to somewhat more that 1/2 a substitution per year. Remember, a substitution is a replacement of one allele for another at a locus on a population wide scale. If this is correct that means right now every few years alleles driven by selection are being fixed within our species.
At the old-school Gene Expression, p-ter posts some analysis and critiques. A great comments section has arisen on this post, including comments from some of the principals, and general comments about the quality of the discussion on blogs compared to the journal process. I've answered some of the points in my rarely asked questions post, but the most powerful part bears repeating:
Every distribution has a tail, so if they were to move their threshold a bit further to the right, surely they'd be able to narrow down the number of regions to something consistent with a constant rate. That is, the entire argument is predicated on perfectly identifying selection in the regions of the parameter space they search. This is a major assumption, and not one I'm willing to make without strong evidence. They provide none.
Actually, with an acceleration of around two orders of magnitude, we can tolerate a lot of slop in the estimates. We don't need to perfectly identify selection -- in fact, we'd still have strong support for rapid acceleration if we threw away 95 percent of our data! Naturally, we don't have to do that -- our methods are based on a threshold that eliminates nearly all false positives, and we are missing the vast majority of events. For one thing, the LDD test doesn't find selection on multiple alleles at the same locus. I am working on new methods that will find some of these kinds of events, but for the time being we continue to interpret all things conservatively.
Andrew Sullivan posts approvingly:
I posted on this potentially world-changing research this afternoon. Here's a helpful, chatty, specialist blog with lots of extra links if you're scientifically literate and curious.
What I want to know is, sure, Razib is helpful and chatty, but what am I, chopped liver?
Larry Moran has added several posts on the research, starting with this one:
In addition to the major flaw in logic, there are many other things wrong with the claim that modern humans have stopped evolving. The claim carries with it a very loaded assumption that is never explicitly stated. The assumption is that humans have pretty much reached their optimal level of fitness for all other characteristics. For example, we are no longer selecting for higher intelligence, or a better immune system, or more efficient energy production, or stronger muscles, or any of a host of other things that might make us better adapted to all environments.
Why is this assumption necessary? Because nobody could possibly suggest that we have stopped evolving without assuming that we have reached optimal fitness for all those things in our present environment.
Larry follows with several other posts, some critical, focused in part on the problem of how much evolution is explained by positive selection as opposed to other forces.
Nature's blog, "The Great Beyond" notes the paper and the resulting discussion.
More will follow...
Why human evolution accelerated
Like most good stories in biology, this one begins with Darwin. Darwin was always very interested in animal breeding, which he considered the best analogy for the process of natural selection. Of course, if you're breeding livestock and want to select for some characteristics, it is important to select from as large a herd as possible, because large populations have more variation in them. Darwin recognized this as an important condition for natural selection, which relies on sufficient variation in natural populations.
[A]s variations manifestly useful or pleasing to man appear only occasionally, the chance of their appearance will be much increased by a large number of individuals being kept.... Hence, number is of the highest importance for success.
These words from the Origin, "number is of the highest importance for success" were influential.
This is a quick review of the research, based on a presentation I gave earlier this year. It is not complete, and glosses a number of very important details. A close reader looking for how to do genomics would be better served reading the actual research paper. Here, I'm trying to express the science for everyone else.
Why accelerated adaptive evolution is faster evolution
RPM at Evolgen has a post raising a concern I've been seeing a lot the last week or two:
If you add up all three classes of mutations -- deleterious, neutral, and beneficial -- and figure out how many have fixed over the time scale you're looking at, you get the amount of evolutionary change along the lineage in question. So, to say that there was increased evolution along the human lineage in recent history implies that there was an increase in the total number of genetic changes. However, an increase in the amount of adaptive evolution (or an increase in the number of mutations fixed by positive selection), means there was an increase in the number of beneficial changes along the human lineage in recent history.
Here's the point in a nutshell:
1. Our recent acceleration paper suggests that the rate of adaptive human evolution has vastly increased during the past 40,000 years.
2. Some people confuse the idea of adaptive evolution with the idea of neutral evolution.
3. We can't let this happen, because, well, choose one: (a) we're good acolytes of Stephen Jay Gould; (b) people might start suggesting that all the human phylogeography based on "neutral" loci is irrelevant or worse; (c) we have a deep concern with the pattern of evolution of gene variants that don't actually do anything interesting.
I tend to notice that the various critiques of acceleration don't include any mathematics. I don't really understand this, since the math is simple. It is a whole lot easier to look at this algebra than to write a four or five-paragraph blog post!
So, let's consider some of the mathematical relations describing neutral evolution and how they apply to the recent increase in human population numbers.
1. The expected change in frequency of a neutral allele each generation is zero. That is, after all, why we call them neutral.
2. But the variance in the change in frequency of a neutral allele is related to population size -- in fact it is p(1 - p)/2Ne, where Ne is the effective population size (actually the variance effective size).
3. Because of this relation, neutral alleles in large populations change more slowly in frequency than those in small populations. Once human populations reached an effective size on the order of 100,000 -- certainly by 40,000 years ago -- the change in allele frequency due to drift alone became extremely small (on the order of 10-6 or less per generation).
4. So neutral evolution in the past 40,000 years should have vastly slowed compared to earlier phases of human evolution.
Except...
5. Changes in population size make absolutely no difference to the neutral substitution rate. The rate of generation of new neutral mutations is directly proportional to population size (2Neu for an autosomal locus). But the rate of fixation is inversely proportional to population size (1/2Ne). So the neutral substitution rate is simply u: the neutral mutation rate, irrespective of population size. That's part of what makes the neutral substitution rate cool -- and of course, what underlies the molecular clock assumption.
6. From this, we might conclude that the rate of neutral evolution was absolutely unchanged in the last 40,000 years. Of course, now it is obvious that the problem is what we mean by "rate" -- do we mean the substitution rate or the per-generation rate of change in allele frequency?
Except...
7. It should be obvious that we don't mean "neutral substitution rate" because this is irrelevant to recent human evolution. The fixation time of a new neutral mutation is directly proportional to the effective size of the population (4Ne generations for an autosomal locus). It doesn't take much figuring to show that is a long, long time from now with today's population size. There is no chance that a new neutral mutation within the last 40,000 years could be near fixation today -- in fact, every neutral segregating allele 40,000 years ago ought to still be segregating today!
8. From that perspective, we might well conclude there has been no neutral evolution in the last 40,000 years -- because it is vanishingly unlikely that any neutral variation has been lost during that time.
Except...
9. Our study actually did find a large number of neutral areas of the genome that had recently approached fixation, and a much larger number of initially rare neutral variants that have reached substantial frequencies during the last 40,000 years. Empirically, neutral evolution has been very rapid during recent human history. This is entirely the result of ...
10. Hitchhiking. The fast rate of generation of new adaptive mutations means that the rate of neutral evolution by hitchhiking has vastly accelerated in the recent past. This is, after all, how we manage to find evidence of selection in the first place -- the hitchhiking effect on neutral markers!
Therefore, the rate of neutral evolution in humans really has accelerated, as a function of hitchhiking on new adaptive mutations. For every selected mutation, we are talking about hundreds of kilobases' worth of linked neutral variants that have been experiencing rapid changes in frequency due to hitchhiking. In the long run, this will have not a jot of effect on the neutral substitution rate, but it accounts for most of the neutral evolution of allele frequencies in human populations.
I expect that there will be people who don't like this idea. I expect many of them have been counting on various neutral markers being informative about population movements. I'm not saying that neutral markers aren't informative, but we really need to consider the effects of selection on these distributions of markers.
Another class of people who don't like this idea are those who propagate one of my pet peeves -- the idea that we need to "invoke" selection as some kind of extraordinary event. The use of this term is very clear: Its only purpose is to vilify folks who want to explain evolution in terms of Darwin's mechanism. It's precisely the same way that we vilify creationists -- they want to "invoke" supernatural forces to explain evolutionary changes.
It's time to get the message -- natural selection has been the major force driving recent human evolution. Humans are no exception to the natural order -- any species that has increased in numbers and changed in ecology to the extent of ours should undergo a rapid pulse of selection resulting in the appearance and proliferation of many more new adaptive mutations. In fact, it looks like domesticated species like maize have undergone a similar effect. There's no "invoking" here, and neutrality is not a hypothesis that can explain these observations.
The foregoing should make one thing very clear -- I have nothing against neutral evolution. I am not an "adaptationist", and have no stakes whatsoever in the "adaptationist-neutralist controversy". This is not a matter of preferences or verbal arguments -- it is simple algebra!
What's more, its pretty obvious that this account of recent neutral evolutionis an evolutionary scenario of which Stephen Jay Gould would have been proud: the most widespread source of change in human genes is chance linkage to a relatively small number of selected sites.
It's just that there are quite a few more of these selected sites than anybody probably expected to find.
Acceleration rarely-asked questions
Usually an FAQ starts with the easiest-to-answer questions. Those are, after all, the ones that are asked frequently!
But today I wanted to handle some of the hardest-to-answer questions: questions about the paper coming from people who are extremely knowledgeable about selection in the genome. We are working on three years of papers describing local and genome-wide scans of positive selection. At this point, the "best" methods each have weaknesses, and our method (the LDD, or "linkage disequilibrium decay" test) is no exception. People who know the weaknesses should be wondering, how have we taken them into account?
In a tight six-page limit, it is impossible to answer every valid question. We accentuated the most obvious ones, but we considered a wide array of others (and dealt with many during peer review). Still, it would be good to have a resource where these issues are hashed out for anyone to read them.
To that end, I've compiled a list of "rarely asked questions": what I see as some of the most critical problems with a study of recent selection like ours, and how we've addressed these in a way that makes our study conservative.
I will be adding to this list as I come across new critiques. And for those who aren't quite conversant with genomic techniques, I will be putting up a frequently asked question list tomorrow!
John Hawks Department of Anthropology
University of Wisconsin—Madison
Copyright © 2007 John Hawks