Evolution of steroid-5 alpha-reductases and comparison of their function with 5 beta-reductase

Steroid-5 alpha-reductases (SRD5 alpha) and steroid-5 beta-reductase (SRD5 beta) represent a convergence in evolution: they share similar biological functions, but do not have a common ancestor. In vertebrates, SRD5 alpha and SRD5 beta are involved in C-19 and C-21 steroid biosynthesis, bile acid biosynthesis and erythropoiesis. We compare and contrast the history, evolution, tissue distribution, enzyme characteristics and biological functions of SRD5 alpha and SRD5 beta and suggest possible future directions for research efforts. Both, the unique and overlapping roles that SRD5 alpha and SRD5 beta play in steroid hormone metabolism, are indicated. We also present the phylogeny of the SRD5 alpha. The main SRD5 alpha subfamilies obtained include, not only the well-known SRD5 alpha type 1, type 2 and type 3, but also the synaptic glycoprotein (GPSN2)/trans-2,3-enoly-CoA reductase group. Phylogenetic analysis indicated that a eukaryotic ancestor likely underwent duplication events to generate these three subfamilies (type 1/2, type 3 and GPSN2 ancestors): both SRD5a, type 1/2 and GPSN2 subfamilies may have evolved by ancient duplication events at the early stage of vertebrate and chordate evolution. (C) 2009 Elsevier Inc. All rights reserved.