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Deleterious mutations

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J. B. S. Haldane

J. B. S. Haldane

Fitness is an easy concept to talk about, but in practice it can be quite slippery. This would seem to contradict John Maynard Smith’s contention that biologists have it easy in comparison to social scientists in the context of game theory, because the bookkeeping is easier since fitness is an obvious currency. In any case, until recently outside of laboratory conditions fitness and its evolutionary genetic converse load have been of theoretical rather than empirical interest. But with genomics, and the ability to detect deleterious alleles to a high degree of precision these old issues have become live anew.

In 2008 a paper came out which reported that Europeans had more genetic load than Africans, Proportionally more deleterious genetic variation in European than in African populations. At the time I recall Greg Cochran was somewhat skeptical on grounds of biomedicine, and some rather unrealistic demographic assumptions (an realistically long bottleneck). The basic finding was simple, because of the “Out of Africa” event Europeans (and presumably all non-Africans) would exhibit a higher load of deleterious alleles because of the reduced power of selection in relation to drift. Over the past seven years that simple result has come under critique, and the first author of the 2008 paper now has a review which resolves the conflicting results, The distribution of deleterious genetic variation in human populations, out (the link is to the preprint, which has been around for a while). The short of it seems to be that the distribution of frequencies of deleterious alleles may differ across populations as a function of demographic history, with the bottleneck and rapid population growth resulted in an excess of rare alleles in non-Africans, but the large population producing more efficacy of selection. The theory itself in the paper is less interesting to me than the conclusion. Here he states:

Future work should include examining empirical patterns of deleterious mutations in other human populations that have differing populations histories, such as different amounts of recent population growth. Studies with large samples of individuals will be particularly helpful as they will be informative regarding how deleterious mutations have behaved during recent times….

Genomics is powerful. For the sort of subtle evolutionary patterns which researchers are trying to sniff out it strikes me that good quality whole genomes in larger numbers across more populations are probably necessary before we can make robust generalizations about humans, let alone other species. Cautious is definitely important because the first wave of SNP-chip results seem to have produced a set of results which were interpreted in light of theory, without understanding that the empirical results were only a sliver of reality constrained by the methods at hand.

• Category: Science • Tags: Deleterious mutations, Population Genetics 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at"