Friday, December 28, 2007

Another comment on Hawks et al

John Hawks has recently published a post commenting on what I thought was a pretty decent post by evolgen, about the rate of adaptative vs neutral evolution. I take issue with a number of points raised in the Hawks post, and in Hawks et al. Firstly, as I discussed previously I think that Hawks et al have not shown a speed up in the rate of selective sweeps. Also there are a number of aspects of the Hawks et al analysis (particularly the cutoff and the inclusion of the parents and children in the HapMap analysis, see the post and comments at gene expression), which are very non-standard and (at least to my knowledge) have not been shown to be appropriately robust, nor seemingly discussed in the paper.

The issue that I want to discuss here, is the one that Hawks raises about the rate of genetic drift having slowed and the rate of sweeps is expected to have increased dramatically in the past 40,000 years. This idea is presumably based on the graph of population size (Fig 2) in Hawks et al, however this graph seems to be of population size rather than effective population size. Though in the paper they seem to be treated interchangeably.

Now the rate of genetic drift and the efficiency of selection in a population is governed by the effective population size. The effective size of a population (Ne) is often much smaller than the census size of the population, as it is affected by the variance in reproductive success between individuals. The effective population size is very hard to predict as it depends on many demographic factors. Ne can be estimated from patterns of genetic diversity, and the long-term estimated effective population size of humans is ~10,000 (similar to many great apes), reflecting the strong effect of genetic drift in the evolutionary history of humans. Now human populations have recently expanded dramatically in size. All else being equal human effective population sizes will have increased as well, but there is no good way of guessing how much they have increased by. For example rapidly fluctuating population sizes, result in a smaller Ne. If the fluctuations are sufficiently rapid, Ne can be approximated by the harmonic mean of the population size over time. Thus Ne is closer to the lowest values taken by the population overtime, rather than the average population size. If the population size increases on average over time but with frequent crashes, the effective population size will also increase but much less dramatically.

The usual (and perhaps only real) way to learn about how Ne has changed through time is to model patterns of genetic diversity, and numerous authors have done this (see for recent example ). The genetic diversity data is consistent with a history of mild recent growth in Bantu-speaking Africans and a moderate strength bottleneck (a burst of genetic drift) into Europe and East Asia.

All this is a long way of saying, the graph of population size increase in Hawks et al, is I think somewhat misleading ( As are Hawks claims "human populations reached an effective size on the order of 100,000 -- certainly by 40,000 years ago"). The graph is of population size estimated from archaeological data, not effective population size. I have no doubt that the effective population size of humans is now large, but when and how this came to be is much harder to tell. The estimation of effective population sizes through time must be from population genetic data. The archaeological data is hopefully a good predictor of average census population size, but can not be taken at face value as a predictor of genetic drift or the rate of selective sweeps, to do this you need to take estimates of the effective population size through time. Now in the estimation of effective population sizes from genetic diversity data can be confounded by selection (if selection is very pervasive), and so perhaps somewhat conservative, but it is the correct approach to take.

Many of the patterns we see in genetic diversity in humans are likely to be the result of genetic drift. Now I have no problem with the idea that the dramatic differences in allele frequencies between population seen at some loci are due to selection. But I believe (and I am willing to change my mind) that the bulk of the patterns seen (eg. the reduction of genetic diversity moving away from Africa) are due to genetic drift not hitch-hiking. Thus the majority of markers are useful for learning about human history, but we should always be careful to consider selection as an alternative explanation.

Hawks post also criticized the phrase 'invoke selection'. I think that invoke is a somewhat charged word (to some people), and perhaps should be avoided. But the fact remains that population genetic test of selection is and will continue to be based on testing for selection by rejecting the null hypothesis of neutral or nearly neutral evolution.


John Hawks said...

I actually have a number of papers discussing the relationship of effective and census population size in human evolution that you may not be aware of. As you note, effective size may be a lot smaller than census size, for many reasons. A Google Scholar search for "effective population size human evolution" will bring up the relevant literature (add "Hawks" to the query to get my papers).

One thing I haven't published is that most of the factors reducing Ne relative to census size should have decreased in force during the last 40,000 years, not increased. For example, one mechanism that I have investigated (e.g., Eller, Hawks and Relethford 2004) is the extinction and recolonization of small subpopulations. This effect may have been very important during much of human evolution and may have reduced effective population sizes by more than tenfold, using reasonable population parameters. But the population structure that enabled this effect had come to an end by the Upper Paleolithic, as evidenced by archaeological evidence for larger, relatively sedentary populations.

Likewise, large climate fluctuations may have caused bottlenecks in the human population, but these could not have reduced population sizes below the level of several millions during the terminal Pleistocene, because we have archaeological evidence showing a pan-Old-World distribution of humans during that entire time span, including in the coldest regions like continental Europe.

When I write that "effective sizes were larger than 100,000 by 40,000 years ago," that is precisely what I mean. The census population size of humans at that time was on the order of millions individuals. Those populations had structures like those of recent hunter-gatherers or small-scale pastoralists, with effective sizes on the order of half to one-third the effective size. Possibly other factors reduced effective sizes further, maybe even 10-fold further. One hundred thousand is absolutely a minimum estimate for their effective size.

This is an estimate, by the way, that appears very conservative in light of the usual genetic estimates for population growth (perhaps 100- to 1000-fold growth before 30,000-70,000 years ago).

I am quite aware of the theoretical difficulties of matching archaeological and historical evidence to genetic models -- as I have some experience in this area. But it is an irritating tendency among geneticists to pretend that we know nothing at all about these ancient populations. We are left with models (like some that have been published recently) in which a global effective population of 10,000 existed up to the present.

Which leaves me wondering, who built the pyramids?

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