mtDNA selection in Iceland?

5 minute read

Leave it to me to have readers unwilling to ignore selection in recent populations! Here’s an e-mail:

Why couldn't the Icelandic genetic changes have been the result of selection that favored some mtDNA lineages rather than others? We know the population of Iceland derived from settlers that were transplanted into a relatively alien climate and ecology, and had to adjust agriculture and subsistence activity to survive there. We know that there were dramatic environmental insults to the population: disease, starvation, eruptions. At least some of these insults would have likely been more severe than the ancestral populations would have encountered, whether they were Scandinavian or "Celtic".
So why isn't there at least a token mention of selection, either by you or by the authors? Is "genetic drift" that much more likely than selection? Is selection a more academically risky proposition than the comforting mathematics of "drift"?

This refers to my post earlier this week about the loss of mtDNA haplotypes from medieval Icelanders. Iceland has around half the number of unique haplotypes that other European samples have, despite similar sampling intensity. I went through some quick simulations of genetic drift in a relatively small, medieval Iceland-sized population to show that the loss of these alleles by drift was quite likely. I also pointed out that very large changes in frequency of common alleles were not a likely outcome of drift, even in the small population. This went along with another post, (“Could genetic drift really break your heart?”), which claimed that a relatively new heart-disease risk mutation was not likely to have become common by genetic drift. In that case, I thought that some selection was probably necessary – both because the South Asian population has been very large for a long time, and because the mutation has a deleterious effect that would impede it from drifting upward.

But showing that genetic drift could explain the Iceland results is not the same as rejecting the hypothesis of selection.

In other ancient European samples, it is pretty clear that selection must explain differences in mtDNA haplotype frequencies over time. Neolithic Germans were dominated by a haplotype that is vanishingly rare in Europe today (“Early European mtDNA: only mysterious if you want it to be”). Similar but less extreme results are also true of medieval British and medieval Danes. All over Europe, some mtDNA haplotypes have been proliferating in the last few thousand years, and others have been declining. That is in accordance with other evidence that mtDNA has been selected in recent populations (Mitochondrial DNA adaptations in living human populations”), as well as the associations of various mtDNA haplotypes with human chronic diseases.

Humans are not exceptional here, either – for example medieval skeletons of Scandinavian dogs show mtDNA selection has happened to them, too.

In the case of Iceland, we have a lot of mtDNA haplotypes that have been lost. It is possible that purifying selection took out some number of these. Probably more likely, positive selection may have increased the frequency of one or more common haplotypes, inevitably reducing the collective frequency of the others. Under that hypothesis, the loss of any particular mtDNA haplotype is a random event, but the fact that an unexpectedly large number were lost would be attributable to selection on common haplotypes.

We could test this hypothesis by considering the frequencies of the more common haplotypes. That would also allow us to examine whether the same mtDNA haplotypes have been favored in other European populations.

In the meantime, the loss of mtDNA haplotypes in Iceland does appear to be consistent with drift, given what we know about Iceland historical demography. That’s the most important part: Genetic drift is not a null hypothesis, it involves many assumptions about demography. When we know information about the demography, we shouldn’t pretend that we don’t.

One final point: Is selection an “academically risky proposition”?

There’s no question that I’m the leading proponent of the idea that natural selection has been widespread, powerful and important in human evolution. I didn’t exactly elbow my way into this position. Very few people were willing to work with the idea that natural selection materially affected human genetic variation. This has given me some success, partly because I’ve been able to test easy and obvious hypotheses that R. A. Fisher might have thought up.

I find all of this to be very puzzling. Why is it, for example, that Rush Limbaugh and the Drudge Report could pick up on the importance of natural selection, but so many human geneticists can’t?

Whatever the reasons, I’ve been talking about mtDNA selection for ten years. I reviewed the issue here in 2005 (“Selection, nuclear genetic variation, and mtDNA”):

Within the past 30,000 to 1 million years, human populations have changed radically in longevity (Caspari and Lee 2004), brain size (Lee and Wolpoff 2003; Ruff et al. 1997), diet, and energetics (Leonard and Robertson 1997; Sorensen and Leonard 2001). Human mtDNA variants have been found to be associated with chronic diseases of aging , brain disorders (Zhu et al. 2004), performance in athletes (Niemi and Majamaa 2005), and longevity itself (Niemi et al. 2005). The present pattern of variation also appears to be correlated with climate (Ruiz-Pesini et al. 2004), and may affect the dietary energetics and insulin metabolism (Lowell and Schulman 2005).
Simply put, variation in mtDNA is a strong target for further research into the effects of aging, metabolism, and disorders of the brain for a reason: it impacts all these areas strongly.

I’ve revisited the issue many times in the last four years. At one point, it got to the stage where I wondered if I was writing about mtDNA selection too much. I wrote:

I'm sure some readers are beginning to think this is mtDNA Selection Central. Believe it or not, I've gotten a lot of requests to cover this topic, which of course is one of the central issues in the Neandertal problem as well as the unraveling of human origins.
And it's an exciting developing story: it shows how medical genetics is steamrolling the human genetics of the past thirty years. Finding mutations that actually do things has great medical interest, and the search is accelerating. This work is being undertaken by people who have no investment in the idea that variation among humans should be completely neutral.
After all, what's more important: that a neutral mtDNA lets us trace human migrations, or that understanding mtDNA selection helps us find treatments for Alzheimer's disease?

Has it hurt my career? Well, I have to admit that some of my colleagues think I’m a total wackaloon. Ten years ago, when I started talking about mtDNA selection, I heard snickers from high-ranking scientists when I ascended the podium. Among other things, I fought peer reviews that said that positive selection in humans must be “rare, if it happens at all.”

All I can say is, if the idea of natural selection has damaged my career, I hope for much more damage like this in the future!