Proteobacterial histidine-biosynthetic pathways are paraphyletic.

In Lactococcus lactis there is a protein, HisZ, in the histidine-biosynthetic operon that exhibits significant sequence identity with histidyl-tRNA synthetase (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 proteobacteria), yet are missing from other bacteria, including mycrobacteria and certain proteobacteria. Phylogenetic analysis of the HisRS and HisRS-like family suggests that the HisZ proteins form a monophyletic group that attaches outside the predominant bacterial HisRS clade. These observations are consistent 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. lactis binds to the ATP-PRPP transferase (HisG) and that both HisZ and HisG are required for catalyzing the first reaction in histidine biosynthesis. Phylogenetic analysis of HisG sequences shows conclusively that proteobacterial HisG and histidinol dehydrogenase (HisD) sequences are paraphyletic and that the partition of the Proteobacteria associated with the presence/absence of HisZ corresponds to that based on HisG and HisD paraphyly. Our results suggest that horizontal gene transfer played an important role in the evolution of the regulation of histidine biosynthesis.