Structural relationships among members of the mammalian sulfotransferase gene family.

Sulfotransferases constitute a superfamily of related enzymes that play critical roles in the regulation of steroid hormone action, neurotransmitter function, detoxification, and carcinogenesis. Understanding the functional relationships among these enzymes has so far been difficult due to their overlapping substrate specificities. To help clarify these relationships, we conducted a thorough and comprehensive molecular phylogenetic analysis of 25 different mammalian sulfotransferase cDNA and gene (St) sequences using maximum parsimony and distance matrix methods. This analysis suggested five distinct gene families: an alcohol/androgen/hydroxysteroid/dehydroepiandrosterone (Std) family, an aryl/minoxidil/phenol (Stp) family, an estrone/estrogen (Ste) family, a thyroid hormone family (St1b1), and a family (St1c1) defined so far only on the basis of its specificity for the carcinogen N-hydroxy-2-acetylaminofluorene. New insights obtained through this study include (1) a bootstrap analysis supporting the reliability of family subgroupings, (2) identification of an insertion that appears to be characteristic of the St1b1 and Stlc1 families, (3) identification of sequences likely to represent paralogs of multigene families, and (4) identification of species likely to contain, or not contain, orthologous multigene families and thus their specialized functions.