Function and molecular evolution of mammalian Sox15, a singleton in the SoxG group of transcription factors

In mammals, the group G of the Sry-related high-mobility-group (HMG) box genes (Sox) contains only one member, Sox15. Comparative genomic analysis of the Sox genes in the B1 and G groups indicates that an ancestral gene may have originated as an intron-containing gene belonging to group B1 and evolved into zebrafish Sox19a/b, Xenopus SoxD, and mammalian Sox15. Although these genes have different names, they are orthologous. The zebrafish and Xenopus orthologues are highly expressed in the central nervous system, whereas mouse Sox15 only shows strong expression in the placenta, an organ characteristic of all mammals except monotremes. Interestingly, Sox15 appears to be a pseudogene in the marsupial opossum. Sox15-deficient mice exhibit delayed skeletal muscle regeneration, indicating that Sox15 plays a crucial role in this process. On the other hand, Xenopus SoxD induces anterior neural development. Thus, there appears to be little functional overlap between Sox15 and its orthologues, Sox19a/b and SoxD. In this review, I discuss the roles of Sox15, its functional redundancy with SoxB1 group members, and its molecular evolution.