Comparative Genomics of Sex-Determination-Related Genes Reveals Shared Evolutionary Patterns Between Bivalves and Mammals, but Not Fruit Flies

The molecular basis of sex determination (SD), while being extensively studied in model organisms, remains poorly understood in many animal groups. Bivalves, a diverse class of molluscs with a variety of reproductive modes, represent an ideal yet challenging clade for investigating SD and the evolution of sexual systems. However, the absence of a comprehensive framework has limited progress in this field, particularly regarding the study of sex-determination-related genes (SRGs). In this study, we performed a genome-wide sequence evolutionary analysis of the Dmrt, Sox and Fox gene families in more than 40 bivalve species. For the first time, we provide an extensive and phylogenetically aware dataset of these SRGs, and we find support for the hypothesis that Dmrt-1L and Sox-H may act as primary sex-determining genes by showing their high levels of sequence diversity within the bivalve genomic context. To validate our findings, we studied the same gene families in two well-characterised systems, mammals and fruit flies (genus Drosophila). In the former, we found that the male sex-determining gene Sry exhibits a pattern of amino acid sequence diversity similar to that of Dmrt-1L and Sox-H in bivalves, consistent with its role as master SD regulator. In contrast, no such pattern was observed among genes of the fruit fly SD cascade, which is controlled by a chromosomic mechanism. Overall, our findings highlight similarities in the sequence evolution of some mammal and bivalve SRGs, possibly driven by a comparable architecture of SD cascades. This work underscores once again the importance of employing a comparative approach when investigating understudied and non-model systems.