The microevolution of V1r vomeronasal receptor genes in mice

Abstract

Vomeronasal sensitivity is important for detecting intraspecific pheromonal cues as well as environmental odorants and is involved in mating, social interaction, and other daily activities of many vertebrates. Two large families of seven-transmembrane G-protein-coupled receptors, V1rs and V2rs, bind to various ligands to initiate vomeronasal signal transduction. Although the macroevolution of V1r and V2r genes has been well characterized throughout vertebrates, especially mammals, little is known about their microevolutionary patterns, which hampers a clear understanding of the evolutionary forces behind the rapid evolutionary turnover of V1r and V2r genes and the great diversity in receptor repertoire across species. Furthermore, the role of divergent vomeronasal perception in enhancing premating isolation and maintaining species identity has not been evaluated. Here we sequenced 44 V1r genes and 25 presumably neutral noncoding regions in 14 wild-caught mice belonging to Mus musculus and M. domesticus, two closely related species with strong yet incomplete reproductive isolation. We found that nucleotide changes in V1rs are generally under weak purifying selection and that only ∼5% of V1rs may have been subject to positive selection that promotes nonsynonymous substitutions. Consistent with the low functional constraints on V1rs, 18 of the 44 V1rs have null alleles segregating in one or both species. Together, our results demonstrate that, despite occasional actions of positive selection, the evolution of V1rs is in a large part shaped by purifying selection and random drift. These findings have broad implications for understanding the driving forces of rapid gene turnovers that are often observed in the evolution of large gene families.

FIG. 1.—

An unrooted tree of 188 putatively functional mouse V1rs (Shi et al. 2005). Red branches denote the 44 V1rs surveyed in this study. Branches denoted with * have putatively functional rat V1r orthologs (Grus and Zhang 2008). Gene family names are from Rodriguez et al. (2002). The tree was reconstructed using the Neighbor-Joining method (Saitou and Nei 1987) with Poisson-corrected protein distances. The scale bar shows 0.1 amino acid substitution per site.

FIG. 2.—

Frequency distributions of Tajima's D and Fu and Li's D* among 44 V1rs and 25 noncoding regions in mouse. (A) Tajima's D in M. musculus; (B) Tajima's D in M. domesticus; (C) Fu and Li's D* in M. musculus; and (D) Fu and Li's D* in M. domesticus.