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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. Here, 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 also 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. These 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] ;  [1]
  1. Center for Research and Advanced Studies of the National Polytechnic Inst., 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, Structural Biology Center
  4. Univ. of Texas Health Science Center, Houston, TX (United States). Dept. of Microbiology and Molecular Genetics
  5. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics
  6. Center for Research and Advanced Studies of the National Polytechnic Inst. (Mexico)
  7. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomi; Univ. of Texas Health Science Center, Houston, TX (United States). Dept. of Microbiology and Molecular Genetics; Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology
Publication Date:
Grant/Contract Number:
AC02-06CH11357; DE017382; GM094585; 132376; 179290
Type:
Accepted Manuscript
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); National Institutes of Health (NIH); National Science Foundation (NSF)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1393154