The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation

Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting bet ween weakly selected alleles, call restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synony mous-site mutations, considering the fate of novel variants ill a two-locus model and the equilibrium effects of interference with multiple loci and r eversible mutation. We find that weak selection Hill-Robertson (wsHR) inter ference can considerably reduce adaptation, e.g., codon bias, and, to a les ser extent, levels of polymorphism, particularly in regions of low recombin ation. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also gene rates specific patterns of linkage disequilibrium. While the selection coef ficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may expl ain the unexpected constancy of codon bias across species of very different census population sizes, as weil as several unusual features of codon usag e in Drosophila.