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natural selection - Humpath.com - Human pathology

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natural selection

Sunday 7 March 2010

Empowered by technology and sampling efforts designed to facilitate genome-wide association mapping, human geneticists are now studying the geography of genetic variation in unprecedented detail.

With high genomic coverage and geographic resolution, these studies are identifying loci with spatial signatures of selection, such as extreme levels of differentiation and correlations with environmental variables.

Collectively, patterns at these loci are beginning to provide new insights into the process of human adaptation.

Deleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In this sense, selection is more "effective" in larger populations.

Studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate.

Variants of Morton, Crow, and Muller’s "total mutational damage" can provide the soundest and most practical basis for such comparisons.

Using simulations, analytical calculations, and 1000 Genomes Project data, authors provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. They show that recent demography has likely modulated the effect of selection and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary data sets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modeling assumptions and is unlikely to provide much biological insight about human populations.

Paywall References

- When Is Selection Effective? Gravel S. Genetics. 2016 May;203(1):451-62. doi : 10.1534/genetics.115.184630 PMID: 27010021

- Spatial patterns of variation due to natural selection in humans. Novembre J, Di Rienzo A. Nat Rev Genet. 2009 Nov;10(11):745-55. PMID: 19823195