Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation

TY - JOUR

T1 - Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation

AU - Peter, Benjamin M.

AU - Huerta-Sanchez, Emilia

AU - Nielsen, Rasmus

PY - 2012/10

Y1 - 2012/10

N2 - An outstanding question in human genetics has been the degree to which adaptation occurs from standing genetic variation or from de novo mutations. Here, we combine several common statistics used to detect selection in an Approximate Bayesian Computation (ABC) framework, with the goal of discriminating between models of selection and providing estimates of the age of selected alleles and the selection coefficients acting on them. We use simulations to assess the power and accuracy of our method and apply it to seven of the strongest sweeps currently known in humans. We identify two genes, ASPM and PSCA, that are most likely affected by selection on standing variation; and we find three genes, ADH1B, LCT, and EDAR, in which the adaptive alleles seem to have swept from a new mutation. We also confirm evidence of selection for one further gene, TRPV6. In one gene, G6PD, neither neutral models nor models of selective sweeps fit the data, presumably because this locus has been subject to balancing selection.

AB - An outstanding question in human genetics has been the degree to which adaptation occurs from standing genetic variation or from de novo mutations. Here, we combine several common statistics used to detect selection in an Approximate Bayesian Computation (ABC) framework, with the goal of discriminating between models of selection and providing estimates of the age of selected alleles and the selection coefficients acting on them. We use simulations to assess the power and accuracy of our method and apply it to seven of the strongest sweeps currently known in humans. We identify two genes, ASPM and PSCA, that are most likely affected by selection on standing variation; and we find three genes, ADH1B, LCT, and EDAR, in which the adaptive alleles seem to have swept from a new mutation. We also confirm evidence of selection for one further gene, TRPV6. In one gene, G6PD, neither neutral models nor models of selective sweeps fit the data, presumably because this locus has been subject to balancing selection.

U2 - 10.1371/journal.pgen.1003011

DO - 10.1371/journal.pgen.1003011

M3 - Journal article

C2 - 23071458

SN - 1553-7390

VL - 8

SP - 1

EP - 14

JO - P L o S Genetics

JF - P L o S Genetics

IS - 10

M1 - e1003011

ER -