TY - JOUR TI - Evolution of substrate specificity in a retained enzyme driven by gene loss AU - Juárez-Vázquez, Ana Lilia AU - Edirisinghe, Janaka N AU - Verduzco-Castro, Ernesto A AU - Michalska, Karolina AU - Wu, Chenggang AU - Noda-García, Lianet AU - Babnigg, Gyorgy AU - Endres, Michael AU - Medina-Ruíz, Sofía AU - Santoyo-Flores, Julián AU - Carrillo-Tripp, Mauricio AU - Ton-That, Hung AU - Joachimiak, Andrzej AU - Henry, Christopher S AU - Barona-Gómez, Francisco A2 - Valencia, Alfonso VL - 6 PY - 2017 DA - 2017/03/31 SP - e22679 C1 - eLife 2017;6:e22679 DO - 10.7554/eLife.22679 UR - https://doi.org/10.7554/eLife.22679 AB - 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. KW - evolution by gene loss KW - genome decay KW - enzyme substrate specificity KW - Actinomyces KW - Histidine and tryprophan biosynthesis KW - phosphoribosyl isomerase A JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -