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The McDonald-Kreitman Test and its Extensions under Frequent Adaptation: Problems and Solutions | | Philipp W. Messer
; Dmitri A. Petrov
; | | Date: |
1 Nov 2012 | | 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 (alpha) from polymorphism and divergence data. We find that in the
presence of slightly deleterious mutations, MK estimates of alpha 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 alpha obtain almost the correct alpha 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 suggest a simple asymptotic extension of the MK test that
should yield accurate estimates of alpha even in the presence of linkage
effects. | | Source: | arXiv, 1211.0060 | | Services: | Forum | Review | PDF | Favorites | |
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