Expression profile and potential functional differentiation of the Speedy/RINGO family in mice

As novel cyclin-dependent kinase (CDK) activators, Speedy/RINGO (hereafter named Speedy) proteins can directly regulate the cell cycle of vertebrates by binding to and activating various CDKs. Previous studies have shown that Speedy genes are highly associated with different types of cancer and other diseases. However, Speedy genes have not been systematically identified in mice, and their function and expression profiles remain elusive, which greatly hinders the functional and mechanistic study of Speedy genes in vivo. Here, we comprehensively identified Speedy genes in the mouse genome. Phylogenetic analysis showed that the Speedy gene family should be divided into three subfamilies, rather than the previously reported two subfamilies. Mice have two of the three subfamilies of Speedy genes, namely, subfamilies A and E. Speedy subfamily C genes have been lost from the mouse genome. By combining experimental and bioinformatics approaches, we found that the genes from subfamilies A and E have different expression profiles, indicating their functional divergence, which was also consistent with the phylogenetic results. The genes belonging to subfamily E showed only slightly different expression profiles, indicating their similar functions. Coexpression network analysis showed that the genes coexpressed with mouse Speedy genes were primarily enriched in reproduction-related mechanisms and there were significant functional differences between genes from subfamilies A and E, further demonstrating functional differentiation. In summary, we provide a comprehensive landscape (from evolution to expression and function) of the Speedy family in mice; we also demonstrate that Speedy genes mainly participate in reproduction-related mechanisms and that they have undergone functional differentiation in mice.