Joint effects of genetic hitchhiking and background selection on neutral variation

Due to relatively high rates of strongly selected deleterious mutations, di rectional selection on favorable alleles (causing hitchhiking effects on li nked neutral polymorphisms) is expected to occur while a deleterious mutati on-selection balance is present in a population. We analyze this interactio n of directional selection and background selection and study their combine d effects on neutral variation, using a three-locus model in which each loc us is subjected to either deleterious, favorable, or neutral mutations. Ave rage heterozygosity is measured by simulations (1) at the stationary state under the assumption of recurrent hitchhiking events and (2) as a transient level after a single hitchhiking event. The simulation results are compare d to theoretical predictions. It is shown that known analytical solutions d escribing the hitchhiking effect without background selection can be modifi ed such that they accurately predict the joint effects of hitchhiking and b ackground on linked, neutral variation. Generalization of these results to a more appropriate multilocus model (such that background selection can occ ur at multiple sites) suggests that, in regions of very low recombination r ates, stationary levels of nucleotide diversity are primarily determined by hitchhiking; whereas in regions of high recombination, background selectio n is the dominant force. The implications of these results on the identific ation and estimation of the relevant parameters of the model are discussed.