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

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 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. Finally, our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [1] ;  [5] ;  [5] ;  [1] ;  [6] ;  [6] ;  [4] ;  [7] ;  [2] ; ORCiD logo [1]
  1. Unidad de Genomica Avanzada (Langebio) Irapuato (Mexico). Evolution of Metabolic Diversity Lab.
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Computing, Environment and Life Sciences Directorate; Univ. of Chicago, IL (United States). Computation Inst.
  3. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division; Argonne National Lab. (ANL), Argonne, IL (United States). Structural Biology Center, Biosciences Division
  4. Univ. of Texas Health Science Center, Houston, TX (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division
  6. Cinvestav-IPN, Mexico City (Mexico)
  7. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division; Univ. of Texas Health Science Center, Houston, TX (United States); Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology
Publication Date:
Grant/Contract Number:
AC02-06CH11357; 132376; 179290; GM094585; 1611952; DE017382
Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Consejo Nacional de Ciencia y Tecnologia (CONACYT); National Science Foundation (NSF); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1352728
Alternate Identifier(s):
OSTI ID: 1352729; OSTI ID: 1393838