Proteobacterial histidine-biosynthetic pathways are paraphyletic

In Lactococcus lactis there is a protein, HisZ, in the histidine-biosynthet ic operon that exhibits significant sequence identity with histidyl-tRNA sy nthetase (HisRS) but does not aminoacylate tRNA. HisRS homologs that, like HisZ, cannot aminoacylate tRNA are represented in a highly divergent set of bacteria (including an aquificale, cyanobacteria, firmicutes, and proteoba cteria), yet are missing from other bacteria, including mycrobacteria and c ertain proteobacteria. Phylogenetic analysis of the HisRS and HisRS-like fa mily suggests that the HisZ proteins form a monophyletic group that attache s outside the predominant bacterial HisRS clade. These observations are con sistent with a model in which the absences of HisZ from bacteria are due to its loss during evolution. It has recently been shown that HisZ from L. la ctis binds to the ATP-PRPP transferase (HisG) and that both HisZ and HisG a re required for catalyzing the first reaction in histidine biosynthesis. Ph ylogenetic analysis of HisG sequences shows conclusively that proteobacteri al HisG and histidinol dehydrogenase (HisD) sequences are paraphyletic and that the partition of the Proteobacteria associated with the presence/absen ce of HisZ corresponds to that based on HisG and HisD paraphyly. Our result s suggest that horizontal gene transfer played an important role in the evo lution of the regulation of histidine biosynthesis.