title: Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck.
abstract: Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in population genetics. On the basis of theoretical analysis and computer simulations, we suggest that this response qualitatively depends on dominance. The number of dominant or additive deleterious alleles per haploid genome is expected to be slightly increased following the bottleneck and re-expansion. In contrast, the number of completely or partially recessive alleles should be sharply reduced. Changes of population size expose differences between recessive and additive selection, potentially providing insight into the prevalence of dominance in natural populations. Specifically, we use a simple statistic, [Formula: see text], where xi represents the derived allele frequency, to compare the number of mutations in different populations, and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. We also provide empirical evidence showing that gene sets associated with autosomal recessive disease in humans may have a BR indicative of recessive selection. Together, these theoretical predictions and empirical observations show that complex demographic history may facilitate rather than impede inference of parameters of natural selection.
authors: Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors: Daniel J
authors: DJ
authors: Balick
authors: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors: Ron
authors: R
authors: Do
authors: Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors: Christopher A
authors: CA
authors: Cassa
authors: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America; Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: David
authors: D
authors: Reich
authors: Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
authors: Shamil R
authors: SR
authors: Sunyaev
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003198:Computer Simulation; D005787:Gene Frequency / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics*; D005828:Genetics, Population / Q000706:statistics & numerical data*; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D011157:Population Dynamics / Q000706:statistics & numerical data*; D012641:Selection, Genetic