Unusual evolution of 11 beta- and 17 beta-hydroxysteroid and retinol dehydrogenases

11 beta-hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17 beta-hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11 beta-hydroxysteroid dehydrogenases and four mammalian 17 beta-hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11 beta- and 17 beta-hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with beta-hydroxybutyrate dehydrogenase, Il-cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17 beta-hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional enzyme on a fourth branch. Pig 17 beta-hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17 beta-hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17 beta-hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11 beta- and 17 beta-hydroxysteroid dehydrogenases.