Unusual evolution of 11β‐ and 17β‐hydroxysteroid and retinol dehydrogenases

11beta-hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17beta-hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11beta-hydroxysteroid dehydrogenases and four mammalian 17beta-hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11beta- and 17beta-hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with beta-hydroxybutyrate dehydrogenase,11-cis-retinol dehydrogenase and retinol dehydrogenase; Type 3 17beta-hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional enzyme on a fourth branch. Pig 17beta-hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17beta-hydroxysteroid dehydrogenases; in which case, the evolution of 17beta-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 11beta- and 17beta-hydroxysteroid dehydrogenases.