Genealogy of regulation of human sex and adrenal function, prostaglandin action, snapdragon and petunia flower colors, antibiotics, and nitrogen fixation: functional diversity from two ancestral dehydrogenases.

Metabolism of steroid hormones by dehydrogenases is an important mechanism for regulating steroid hormone action. Analysis of recently reported amino acid sequences of 11 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase, and 3 alpha, 20 beta-hydroxysteroid dehydrogenase reveals that they are descended from a common ancestor. Unexpectedly, this superfamily of dehydrogenases has other interesting relatives: 15-hydroxyprostaglandin dehydrogenase, proteins found in nitrogen-fixing bacteria, and enzymes important in the synthesis of antibiotics. The novel lineage of these proteins and the actions of flavonoids in regulating gene transcription in nitrogen-fixing bacteria and mammals provide new insights into the evolution of regulation of gene transcription by intercellular signals in multicellular animals.