Gene buddies: linked balanced polymorphisms reinforce each other even in the absence of epistasis

Abstract

The fates of genetic polymorphisms maintained by balancing selection depend on evolutionary dynamics at linked sites. While coevolution across linked, epigenetically-interacting loci has been extensively explored, such supergenes may be relatively rare. However, genes harboring adaptive variation can occur in close physical proximity while generating independent effects on fitness. Here, I present a model in which two linked loci without epistasis are both under balancing selection for unrelated reasons. Using forward-time simulations, I show that recombination rate strongly influences the retention of adaptive polymorphism, especially for intermediate selection coefficients. A locus is more likely to retain adaptive variation if it is closely linked to another locus under balancing selection, even if the two loci have no interaction. Thus, two linked polymorphisms can both be retained indefinitely even when they would both be lost to drift if unlinked. While these results may be intuitive, they have important implications for genetic architecture: clusters of mutually reinforcing genes may underlie phenotypic variation in natural populations, and such genes cannot be assumed to be functionally associated. Future studies that measure selection coefficients and recombination rates among closely linked genes will be fruitful for characterizing the extent of this phenomenon.