期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 21, 页码 8615-8620出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1220835110
关键词
-
资金
- National Institutes of Health [R01GM100366, R01GM097415, R01GM089926]
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 (a) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates of a 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 a obtain almost the correct a 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 a in our simulations and should provide a fruitful direction for future studies.
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