Evolution of substrate specificity in a retained enzyme driven by gene loss
- Evolution of Metabolic Diversity Laboratory, Mexico
- Argonne National Laboratory, United States
- University of Texas Health Science Cent, United States
- Weizmann Institute of Science, Israel
- University of California, Berkeley, United States
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
- Centro de Investigación en Matemáticas, Mexico
- University of Texas Health Science Center, United States
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.
Data availability
-
The Whole Genome Shotgun (WGS) A. oris MG-1 projectPublicly available at the NCBI Nucleotide (accession no: MAUB00000000).
-
Actinomyces oris strain:MG-1 Genome sequencing and assemblyPublicly available at the NCBI BioProject (accession no: PRJNA327886.
-
Actinomycetaceae Phylogenomics: Comparative Analysis of ModelsPublicly available, subject to registering an account, at KBase (accession no: ws.17193.obj.1).
Article and author information
Author details
Francisco Barona-Gómez
Funding
Consejo Nacional de Ciencia y Tecnología (132376,179290)
- Ana Lilia Juárez-Vázquez
- Ernesto A Verduzco-Castro
- Julián Santoyo-Flores
- Mauricio Carrillo-Tripp
National Institutes of Health (GM094585)
- Karolina Michalska
- Gyorgy Babnigg
- Michael Endres
- Andrzej Joachimiak
US Department of Energy (DE-AC02-06CH11357)
- Andrzej Joachimiak
- Christopher S Henry
National Science Foundation (1611952)
- Janaka E Edirisinghe
- Christopher S Henry
National Institute of Dental and Craniofacial Research (DE017382)
- Chenggang Wu
- Hung Ton-That
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 3,124
- views
-
- 540
- downloads
-
- 22
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Evolution of substrate specificity in a retained enzyme driven by gene loss
eLife 6:e22679.
https://doi.org/10.7554/eLife.22679
Further reading
-
- Biochemistry and Chemical Biology
The biosynthesis of cyclic 3′,5′-adenosine monophosphate (cAMP) by mammalian membrane-bound adenylyl cyclases (mACs) is predominantly regulated by G-protein-coupled receptors (GPCRs). Up to now the two hexahelical transmembrane domains of mACs were considered to fix the enzyme to membranes. Here, we show that the transmembrane domains serve in addition as signal receptors and transmitters of lipid signals that control Gsα-stimulated mAC activities. We identify aliphatic fatty acids and anandamide as receptor ligands of mAC isoforms 1–7 and 9. The ligands enhance (mAC isoforms 2, 3, 7, and 9) or attenuate (isoforms 1, 4, 5, and 6) Gsα-stimulated mAC activities in vitro and in vivo. Substitution of the stimulatory membrane receptor of mAC3 by the inhibitory receptor of mAC5 results in a ligand inhibited mAC5–mAC3 chimera. Thus, we discovered a new class of membrane receptors in which two signaling modalities are at a crossing, direct tonic lipid and indirect phasic GPCR–Gsα signaling regulating the biosynthesis of cAMP.
-
- Biochemistry and Chemical Biology
The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins, combined with the exposure of their residues, accounts for this sensitivity. One context in which IDPs play important roles that are concomitant with massive changes to the intracellular environment is during desiccation (extreme drying). The ability of organisms to survive desiccation has long been linked to the accumulation of high levels of cosolutes such as trehalose or sucrose as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat-soluble (CAHS) proteins. Despite knowing that IDPs play important roles and are co-enriched alongside endogenous, species-specific cosolutes during desiccation, little is known mechanistically about how IDP-cosolute interactions influence desiccation tolerance. Here, we test the notion that the protective function of desiccation-related IDPs is enhanced through conformational changes induced by endogenous cosolutes. We find that desiccation-related IDPs derived from four different organisms spanning two LEA protein families and the CAHS protein family synergize best with endogenous cosolutes during drying to promote desiccation protection. Yet the structural parameters of protective IDPs do not correlate with synergy for either CAHS or LEA proteins. We further demonstrate that for CAHS, but not LEA proteins, synergy is related to self-assembly and the formation of a gel. Our results suggest that functional synergy between IDPs and endogenous cosolutes is a convergent desiccation protection strategy seen among different IDP families and organisms, yet the mechanisms underlying this synergy differ between IDP families.
