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
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The Whole Genome Shotgun (WGS) A. oris MG-1 projectPublicly available at the NCBI Nucleotide (accession no: MAUB00000000).
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Actinomyces oris strain:MG-1 Genome sequencing and assemblyPublicly available at the NCBI BioProject (accession no: PRJNA327886.
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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.
Reviewing Editor
- Alfonso Valencia, Barcelona Supercomputing Center - BSC, Spain
Version history
- Received: October 25, 2016
- Accepted: March 25, 2017
- Accepted Manuscript published: March 31, 2017 (version 1)
- Version of Record published: April 25, 2017 (version 2)
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.
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Evolution of substrate specificity in a retained enzyme driven by gene loss
eLife 6:e22679.
https://doi.org/10.7554/eLife.22679
Further reading
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- Biochemistry and Chemical Biology
- Cell Biology
Numerous lipids are heterogeneously distributed among organelles. Most lipid trafficking between organelles is achieved by a group of lipid transfer proteins (LTPs) that carry lipids using their hydrophobic cavities. The human genome encodes many intracellular LTPs responsible for lipid trafficking and the function of many LTPs in defining cellular lipid levels and distributions is unclear. Here, we created a gene knockout library targeting 90 intracellular LTPs and performed whole-cell lipidomics analysis. This analysis confirmed known lipid disturbances and identified new ones caused by the loss of LTPs. Among these, we found major sphingolipid imbalances in ORP9 and ORP11 knockout cells, two proteins of previously unknown function in sphingolipid metabolism. ORP9 and ORP11 form a heterodimer to localize at the ER-trans-Golgi membrane contact sites, where the dimer exchanges phosphatidylserine (PS) for phosphatidylinositol-4-phosphate (PI(4)P) between the two organelles. Consequently, loss of either protein causes phospholipid imbalances in the Golgi apparatus that result in lowered sphingomyelin synthesis at this organelle. Overall, our LTP knockout library toolbox identifies various proteins in control of cellular lipid levels, including the ORP9-ORP11 heterodimer, which exchanges PS and PI(4)P at the ER-Golgi membrane contact site as a critical step in sphingomyelin synthesis in the Golgi apparatus.
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- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
The mechanism underlying the preferential and cooperative binding of cofilin and the expansion of clusters toward the pointed-end side of actin filaments remains poorly understood. To address this, we conducted a principal component analysis based on available filamentous actin (F-actin) and C-actin (cofilins were excluded from cofilactin) structures and compared to monomeric G-actin. The results strongly suggest that C-actin, rather than F-ADP-actin, represented the favourable structure for binding preference of cofilin. High-speed atomic force microscopy explored that the shortened bare half helix adjacent to the cofilin clusters on the pointed end side included fewer actin protomers than normal helices. The mean axial distance (MAD) between two adjacent actin protomers along the same long-pitch strand within shortened bare half helices was longer (5.0–6.3 nm) than the MAD within typical helices (4.3–5.6 nm). The inhibition of torsional motion during helical twisting, achieved through stronger attachment to the lipid membrane, led to more pronounced inhibition of cofilin binding and cluster formation than the presence of inorganic phosphate (Pi) in solution. F-ADP-actin exhibited more naturally supertwisted half helices than F-ADP.Pi-actin, explaining how Pi inhibits cofilin binding to F-actin with variable helical twists. We propose that protomers within the shorter bare helical twists, either influenced by thermal fluctuation or induced allosterically by cofilin clusters, exhibit characteristics of C-actin-like structures with an elongated MAD, leading to preferential and cooperative binding of cofilin.
