Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans
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- dc.contributor.author Weghorn, Donate
- dc.contributor.author Balick, Daniel J.
- dc.contributor.author Cassa, Christopher
- dc.contributor.author Kosmicki, Jack A.
- dc.contributor.author Daly, Mark J.
- dc.contributor.author Beier, David R.
- dc.contributor.author Sunyaev, Shamil R.
- dc.date.accessioned 2019-09-12T11:15:28Z
- dc.date.issued 2019
- dc.description.abstract The fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein-truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of PTVs under a simple deterministic mutation-selection balance, as has been proposed earlier (Cassa et al. 2017). Here, we investigated the limits of this approximation using both computer simulations and data-driven approaches. Our simulations rely on a model of demographic history estimated from 33,370 individual exomes of the Non-Finnish European subset of the ExAC data set (Lek et al. 2016). Additionally, we compared the African and European subset of the ExAC study and analyzed de novo PTVs. We show that the mutation-selection balance model is applicable to the majority of human genes, but not to genes under the weakest selection.
- dc.format.mimetype application/pdf
- dc.identifier.citation Weghorn D, Balick DJ, Cassa C, Kosmicki JA, Daly MJ, Beier DR et al. Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans. Mol Biol Evol. 2019;36(8):1701-10. DOI: 10.1093/molbev/msz092
- dc.identifier.doi http://dx.doi.org/10.1093/molbev/msz092
- dc.identifier.issn 0737-4038
- dc.identifier.uri http://hdl.handle.net/10230/42267
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Molecular Biology and Evolution. 2019;36(8):1701-10
- dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in Molecular biology and evolution following peer review. The version of record Weghorn D, Balick DJ, Cassa C, Kosmicki JA, Daly MJ, Beier DR, Sunyaev SR. Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans. Mol Biol Evol. 2019; 36(8):1701-1710 is available online at: https://doi.org/10.1093/molbev/msz092
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Protein-truncating variants
- dc.subject.keyword Selection inference
- dc.subject.keyword Genetic drift
- dc.title Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion