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Proc Natl Acad Sci U S A. 2013 May 21;110(21):8615-20. doi: 10.1073/pnas.1220835110. Epub 2013 May 6.

Frequent adaptation and the McDonald-Kreitman test.

Author information

1
Department of Biology, Stanford University, Stanford, CA 94305, USA. messer@stanford.edu

Abstract

Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection (α) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates of α severely underestimate the true rate of adaptation even if all polymorphisms with population frequencies under 50% are excluded. Furthermore, already under intermediate rates of adaptation, genetic draft substantially distorts the site frequency spectra at neutral and functional sites from the expectations under mutation-selection-drift balance. MK-type approaches that first infer demography from synonymous sites and then use the inferred demography to correct the estimation of α obtain almost the correct α in our simulations. However, these approaches typically infer a severe past population expansion although there was no such expansion in the simulations, casting doubt on the accuracy of methods that infer demography from synonymous polymorphism data. We propose a simple asymptotic extension of the MK test that yields accurate estimates of α in our simulations and should provide a fruitful direction for future studies.

PMID:
23650353
PMCID:
PMC3666677
DOI:
10.1073/pnas.1220835110
[Indexed for MEDLINE]
Free PMC Article

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