Gene Duplication, Translocation, and Molecular Evolution of Dmrt1 and Related Sex-Determining Genes in Anurans.

Abstract

Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, birds, and Drosophila, most anurans (frogs and toads) maintain homomorphic sex chromosomes that exhibit a rapid turnover, even among closely related species. Master sex-determining genes evolve via gene duplication or via allelic diversification, and sex chromosome turnover is driven by gene translocation or novel mutations in the existing genes involved in the sexual developmental pathway. To uncover the mechanisms underlying the emergence of master sex-determining genes and sex chromosome turnover, we analyzed 53 published anuran genomes and one caecilian genome (>200 Mya divergence) and available transcriptomes. We asked how often master sex-determining genes arise by gene duplication, whether and how often gene translocation associates with sex chromosome turnover, and if master sex-determining genes evolve under positive selection. We find that chromosome-level synteny is remarkably conserved, with only a few fusions or fissions and no evidence for translocation of four candidate master sex-determining genes (Dmrt1, Foxl2, Bod1l, and Sox3). Only Dmrt1 duplicated in 3 out of 50 species (excluding tetraploid Xenopus), and it showed strong testis-biased expression in all 8 species with available gonadal expression data. While Dmrt1 has evolved under purifying selection, Dmrt1 duplicates exhibit elevated nonsynonymous substitution rates and tendency towards positive selection. Lineage-specific amino acid changes were observed in the conserved DM domain of Dmrt1. These results demonstrate that, in anurans, master sex-determining genes rarely arise via gene duplication, and more likely evolve via allelic diversification. Sex chromosome turnover is not associated with gene translocation and is more likely driven by mutations on genes involved in sexual developmental pathways. All candidate sex-determining genes were under strong purifying selection, with the exception of duplications which are linked to positive selection. Our results suggest future research on anuran sex determination and sex chromosome evolution should focus on identifying allelic diversification and novel mutations on genes involved in sexual developmental pathways.