Phylogenies of glutathione transferase families

The best known glutathione transferase family, with its class-alpha, -mu, -pi, -omega, -sigma, -theta, and -zeta subdivisions, is only one of four, or perhaps five, ancient protein families that conjugate glutathione or use a glutathione intermediate: (1) the cytoplasmic family, (2) the mitochondrial (kappa) family, (3) the microsomal (MAPEG) family, which may actually be two separate families, and (4) the fosphomycin/glyoxalase family. Although the cytoplasmic family is perhaps the most diverse, all four of these families have homologs in both prokaryotes and eukaryotes; it is striking that at least three, and perhaps as many as five, different protein folds capable of binding and positioning glutathione for a nucleophilic attack emerged more than 2 billion years ago. This chapter presents phylogenies for the four (or five) glutathione transferase families, focusing on the statistical evidence for homology (and non-homology).