The Sry gene and reductionism in molecular biology: How to move from the benchtop to a systems approach

The protein Sry has been studied for over twenty years, with much focus on its role in sex determination. Recent evidence suggests that it has multiple functions outside of testis determination. Comparing Sry throughout evolution, from its duplication of copies in a single species (such as in Rattus norvegicus), to its evolution in all of mammals, to how it is homologous to the SOX protein family, has helped to elucidate that the Sry protein has likely evolved to function in other pathways outside testis determination. One of the pathways Sry is suggested to function on is the renin-angiotensin system and thus has a potential to regulate blood pressure. The work with Sry and the Sox proteins was aided by a sequence-to-structure-tofunction approach, which was additionally applied to several other proteins, such as proteins of the renin-angiotensin system, the KRAB domain, SNAIL, and Leptin. These show the potential for such an approach and encourage its usage in more molecular research.