Published March 31, 2017 | Version v1
Journal article Open

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

Description

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.

Data availability

The following data sets were generated:

Juárez-Vázquez AL Barona-Gomez F (2016) The Whole Genome Shotgun (WGS) A. oris MG-1 project Publicly available at the NCBI genome database (accession no: PRJNA327886). https://www.ncbi.nlm.nih.gov/bioproject/PRJNA327886

Michalska K Verduzco-Castro EA Babnigg G Enders M Barona-Gomez F Joachimiak A (2016) Crystal structure of PriA from Actinomyces urogenitalis Publicly available at the RCSB Protein Data Bank (accession no: 4X2R). http://www.rcsb.org/pdb/explore.do?structureId=4X2R

The following previously published data sets were used:

Juarez-Vazquez AL Barona-Gomez F Henry CS (2016) Actinomycetaceae Phylogenomics: Comparative Analysis of Models Publicly available, subject to registering an account at KBase (accession no: ws.17193.obj.1). https://narrative.kbase.us/narrative/ws.17193.obj.1

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Additional details

Identifiers

DOI
10.7554/eLife.22679
Other
oai:uchicago.tind.io:9981

Funding

Consejo Nacional de Ciencia y Tecnología
179290
National Science Foundation
1611952
National Institutes of Health
GM094585
National Institute of Dental and Craniofacial Research
DE017382
Consejo Nacional de Ciencia y Tecnología
132376
U.S. Department of Energy
DE-AC02-06CH11357

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Biochemistry and Molecular Biology