title: Resolving the Conflict Between Associative Overdominance and Background Selection.
abstract: In small populations, genetic linkage between a polymorphic neutral locus and loci subject to selection, either against partially recessive mutations or in favor of heterozygotes, may result in an apparent selective advantage to heterozygotes at the neutral locus (associative overdominance) and a retardation of the rate of loss of variability by genetic drift at this locus. In large populations, selection against deleterious mutations has previously been shown to reduce variability at linked neutral loci (background selection). We describe analytical, numerical, and simulation studies that shed light on the conditions under which retardation vs. acceleration of loss of variability occurs at a neutral locus linked to a locus under selection. We consider a finite, randomly mating population initiated from an infinite population in equilibrium at a locus under selection. With mutation and selection, retardation occurs only when S, the product of twice the effective population size and the selection coefficient, is of order 1. With S >> 1, background selection always causes an acceleration of loss of variability. Apparent heterozygote advantage at the neutral locus is, however, always observed when mutations are partially recessive, even if there is an accelerated rate of loss of variability. With heterozygote advantage at the selected locus, loss of variability is nearly always retarded. The results shed light on experiments on the loss of variability at marker loci in laboratory populations and on the results of computer simulations of the effects of multiple selected loci on neutral variability.
authors.affiliation: Centre for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, EH9 3FL, United Kingdom Brian.Charlesworth@ed.ac.uk.
authors.forename: Brian
authors.identifier: 0000-0002-2706-355X
authors.initials: B
authors.lastname: Charlesworth
mesh_terms: D003198:Computer Simulation; D040961:Genetic Drift; D008040:Genetic Linkage; D005828:Genetics, Population; D006579:Heterozygote; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D011156:Population Density; D011995:Recombination, Genetic; D012641:Selection, Genetic / Q000235:genetics*
keywords: associative overdominance; background selection; deleterious mutations; heterozygote advantage; neutral variability