title: Evolution of substrate specificity in a retained enzyme driven by gene loss.
abstract: 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 orpriAgene, at which these pathways converge, appears to coevolve with the occurrence oftrpandhisgenes. 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.
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Ana Lilia
authors.initials: AL
authors.lastname: Juárez-Vázquez
authors.affiliation: Computing, Environment and Life Sciences Directorate, Argonne National Laboratory, Lemont, United States.|Computation Institute, University of Chicago, Chicago.
authors.forename: Janaka N
authors.initials: JN
authors.lastname: Edirisinghe
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Verduzco-Castro
authors.affiliation: Midwest Center for Structural Genomics, Biosciences Division, Argonne National Laboratory, Lemont, United States.|Structural Biology Center, Biosciences Division, Argonne National Laboratory, Lemont, United States.
authors.forename: Karolina
authors.initials: K
authors.lastname: Michalska
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, United States.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Wu
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Lianet
authors.initials: L
authors.lastname: Noda-García
authors.affiliation: Midwest Center for Structural Genomics, Biosciences Division, Argonne National Laboratory, Lemont, United States.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Babnigg
authors.affiliation: Midwest Center for Structural Genomics, Biosciences Division, Argonne National Laboratory, Lemont, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Endres
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Sofía
authors.initials: S
authors.lastname: Medina-Ruíz
authors.affiliation: Cinvestav-IPN, , Mexico.
authors.forename: Julián
authors.initials: J
authors.lastname: Santoyo-Flores
authors.affiliation: Cinvestav-IPN, , Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Carrillo-Tripp
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, United States.
authors.forename: Hung
authors.initials: H
authors.lastname: Ton-That
authors.affiliation: Midwest Center for Structural Genomics, Biosciences Division, Argonne National Laboratory, Lemont, United States.|Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, United States.|Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: Computing, Environment and Life Sciences Directorate, Argonne National Laboratory, Lemont, United States.|Computation Institute, University of Chicago, Chicago.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Henry
authors.affiliation: Evolution of Metabolic Diversity Laboratory, Unidad de Genómica Avanzada (Langebio), Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Francisco
authors.identifier: 0000-0003-1492-9497
authors.initials: F
authors.lastname: Barona-Gómez
mesh_terms: D000191:Actinomycetaceae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D000220:Adaptation, Biological; D019747:Aldose-Ketose Isomerases / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D017353:Gene Deletion; D009154:Mutation; D013379:Substrate Specificity
chemical_list: D019747:Aldose-Ketose Isomerases; C022548:ribosephosphate isomerase
keywords: Actinomyces; Histidine and tryprophan biosynthesis; biochemistry; enzyme substrate specificity; evolution by gene loss; evolutionary biology; genome decay; genomics; human; phosphoribosyl isomerase A