The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.
Bibliographical noteFunding Information:
We acknowledge Nelly Selem-Mójica, Víctor Villa-Moreno, José-Luis Steffani-Vallejo and Christian E. Martínez-Guerrero for bioinformatics support. We thank Sean Rovito and Angélica Cibrián-Jaramillo for useful comments and evolutionary discussions. We thank members of the Structural Biology Center at Argonne National Laboratory for data collection support. This work was supported by CONACYT Mexico, via grants 132376 to MCT and 179290 to FBG, as well as a scholarships to AJV. And by The National Institutes of Health, grant GM094585 to AJ, the U.S. Department of Energy, under contract DE-AC02-06CH11357, and the National Science Foundation NSF, grant 1611952 to CSH, and the National Institute of Dental and Craniofacial Research of the National Institutes of Health, grant DE017382, to HTT.
© Juárez-Vázquez et al.