Evolution of substrate specificity in a retained enzyme driven by gene loss

• DOI: 10.7554/elife.22679
• Publication Date: 2017-03-31T12:08:58Z
• Authors: Ana Lilia Juárez-...; Janaka N Edirisinghe; Ernesto A Verduzc...; Karolina Michalska; Chenggang Wu; Lianet Noda-García; Gyorgy Babnigg; Michael Endres; Sofía Medina-Ruíz; Julián Santoyo-Fl...; Mauricio Carrillo...; Hung Ton-That; Andrzej Joachimiak; Christopher S Henry; Francisco Barona-...
• Keywords: 0301 basic medicine; 570; Biomedical and clinical sciences; Evolution; QH301-705.5; Science; Bioinformatics and Computational Biology; evolution by gene loss; Adaptation, Biological; Histidine and tryprophan biosynthesis; Biochemistry; Substrate Specificity; Evolution, Molecular; 03 medical and health sciences; Genetics; genomics; biochemistry; genome decay; enzyme substrate specificity; Actinomyces; human; Adaptation; Biology (General); Aldose-Ketose Isomerases; 0303 health sciences; Human Genome; evolutionary biology; Q; R; Molecular; Health sciences; Biological Sciences; Biological; 3. Good health; Biological sciences; phosphoribosyl isomerase A; Actinomycetaceae; Mutation; Medicine; Biochemistry and Cell Biology; Gene Deletion; Biotechnology

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.