In silico sequence analysis of arylamine N-acetyltransferases: evidence for an absence of lateral gene transfer from bacteria to vertebrates and first description of paralogs in bacteria.

The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes responsible for the biotransformation of various arylamine and heterocyclic amines, including drugs and carcinogenic compounds. NAT and NAT-like genes have been identified in several vertebrate and eubacterial species. Little is known about their evolutionary history, but the horizontal transfer of NAT genes from bacteria to vertebrates was recently suggested [S. Salzberg, O. White, J. Peterson, J. Eisen, Science 292 (2001) 1903]. We used various bioinformatics-based approaches to screen eukaryotic and prokaryotic genomes. We identified Mesorhizobium loti NAT genes as the first examples of NAT paralogs in prokaryotes. As shown for vertebrate species, the existence of NAT paralogs in this bacterium may be accounted for by enzymatic specialization after gene duplication. Phylogenetic analysis following the identification of a NAT ortholog in the nonvertebrate species Ciona intestinalis indicated that NAT genes are unlikely to be examples of direct horizontal gene transfer (HGT). Our study suggests that NAT genes have evolved from a common ancestor, with a succession of nonvertebrate intermediates. The absence of NAT genes in yeast, nematode worms, fruit flies, and mustard weed may result from gene loss in these nonvertebrate lineages. These results provide new insight into the taxonomic distribution and evolutionary history of this class of drug-metabolizing enzymes. Copyright 2002 Elsevier Science (USA).