Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

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

  • Author(s): Juárez-Vázquez, Ana Lilia
  • Edirisinghe, Janaka N
  • Verduzco-Castro, Ernesto A
  • Michalska, Karolina
  • Wu, Chenggang
  • Noda-García, Lianet
  • Babnigg, Gyorgy
  • Endres, Michael
  • Medina-Ruíz, Sofía
  • Santoyo-Flores, Julián
  • Carrillo-Tripp, Mauricio
  • Ton-That, Hung
  • Joachimiak, Andrzej
  • Henry, Christopher S
  • Barona-Gómez, Francisco
  • et al.
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 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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View