Epistatic selection in a multi-locus Levene model and implications for linkage disequilibrium

Abstract

We analyze a multiple-locus extension of the Levene (1953) model of population subdivision. We show that stable or quasistable linkage disequilibrium between two selected loci can be maintained even with free recombination, provided that there is a strong enough epistatic interaction. We then consider the dynamics of a third neutral locus and show that its approach to linkage equilibrium depends on the recombination rates and the selection intensities. There is an embedding or hitchhiking effect that extends the time during which a neutral locus which is closely linked to one of the selected loci remains in disequilibrium with both selected loci. Therefore, strong disequilibrium between two loci does not necessarily indicate that those loci are themselves selected, but it does indicate that there is strong selection acting at least on nearby loci. This property implies a warning that screening for linkage disequilibrium as a tool to identify functionally important sites in a genome can be misleading.