Neutral genetic diversity during selective sweeps in nonrecombining populations

Abstract

Selective sweeps, resulting from the spread of beneficial, neutral, or deleterious mutations through a population, shape patterns of genetic variation at linked neutral sites. While many theoretical, computational, and statistical advances have been made in understanding the genomic signatures of selective sweeps in recombining populations, relatively less is understood in populations with little/no recombination, and arbitrary dominance and inbreeding. Using diffusion theory, we obtain the full expression for the expected site frequency spectrum (SFS) at linked neutral sites immediately post and during the fixation of moderately or strongly beneficial mutations. When a single hard sweep occurs, the SFS decays as 1/x for low derived allele frequencies (x), similar to the neutral SFS at equilibrium, whereas at higher derived allele frequencies, it follows a 1/x2 power law as also seen in a rapidly expanding neutral population. We show that these power laws are universal in the sense that they are independent of the dominance and inbreeding coefficients, and also characterize the SFS during the sweep. Additionally, we find that the derived allele frequency where the SFS shifts from the 1/x to 1/x2 power law is inversely proportional to the selection strength; thus under strong selection, the SFS follows the 1/x2 dependence for most allele frequencies. When clonal interference is pervasive, the SFS immediately post-fixation becomes U-shaped and can be approximated by the equilibrium SFS of selected sites. Our results will be important in developing statistical methods to infer the timing and strength of recent selective sweeps in asexual populations, genomic regions that lack recombination, and clonally propagating tumor populations.

Keywords: clonal interference; diffusion theory; dominance; hitchhiking; inbreeding; no recombination; selective sweeps; site frequency spectrum.