Evolution, classification, structure, and functional diversification of steroid 5 α-reductase family in eukaryotes

Steroid 5 alpha-reductase1/2 (SRD5A1/2) is an androgen protein that resembles the plant DET2 and is responsible for the conversion of testosterone to the more active dihydrotestosterone (DHT). Both proteins share functional homology and have a common ancestor. In mammals, the SRD5A1/2 can reduce a wide range of steroid substrates, such as testosterone, progesterone, and aldosterone, by reducing the Delta 4 in ring A. The plant DET2 catalyzes the conversion of campesterol (CR) to campestanol (CN) by reducing the Delta 5 in ring B during brassinosteroid (BRs) biosynthesis. We compared the evolution, structural, and functional homology of the SRD5A family and tried to identify the origin and functional diversification of duplicated genes in eukaryotes. We presented a detailed phylogeny that includes representative species from all eukaryotic groups. Our study indicated that protist is a common ancestor for all the subgroups of the SRD5A family. However, not all protists possess SRD5A1/2/DET2 or other homologs, suggesting that some protists may have lost these gene families during evolution. Lineage-specific duplication leads Caenorhabditis elegance to have three SRD5A1/2 genes but none was found in Drosophila melanogaster. We also identified a new subclass, DET2-like (DET2L), in plants that closely resemble SRD5A1/2/DET2. The hypothesized reductase DET2L showed no phenotypic enhancement when expressed in Arabidopsis det2 mutants, suggesting its possible role in the reduction of polyprenol or other substrates.