Loss of protein synthesis quality control in host-restricted organisms

Melnikov, Sergey V.; van den Elzen, Antonia; Stevens, David L.; Thoreen, Carson C.; Söll, Dieter

doi:10.1073/pnas.1815992115

Title: Loss of protein synthesis quality control in host-restricted organisms

Abstract

Intracellular organisms, such as obligate parasites and endosymbionts, typically possess small genomes due to continuous genome decay caused by an environment with alleviated natural selection. Previously, a few species with highly reduced genomes, including the intracellular pathogens Mycoplasma and Microsporidia, have been shown to carry degenerated editing domains in aminoacyl-tRNA synthetases. These defects in the protein synthesis machinery cause inaccurate translation of the genetic code, resulting in significant statistical errors in protein sequences that are thought to help parasites to escape immune response of a host. In this study we analyzed 10,423 complete bacterial genomes to assess conservation of the editing domains in tRNA synthetases, including LeuRS, IleRS, ValRS, ThrRS, AlaRS, and PheRS. We found that, while the editing domains remain intact in free-living species, they are degenerated in the overwhelming majority of host-restricted bacteria. Our work illustrates that massive genome erosion triggered by an intracellular lifestyle eradicates one of the most fundamental components of a living cell: the system responsible for proofreading of amino acid selection for protein synthesis. Finally, this finding suggests that inaccurate translation of the genetic code might be a general phenomenon among intercellular organisms with reduced genomes.

Authors:

Melnikov, Sergey V. ^[1]; van den Elzen, Antonia ^[2]; Stevens, David L. ^[3]; Thoreen, Carson C. ^[2];

^[4]

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511,
Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520,
Department of Chemistry, Yale University, New Haven, CT 06511
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511,, Department of Chemistry, Yale University, New Haven, CT 06511

Publication Date:: Mon Nov 19 00:00:00 EST 2018

Research Org.:: Yale Univ., New Haven, CT (United States)

Sponsoring Org.:: USDOE Office of Science (SC); National Institutes of Health (NIH)

OSTI Identifier:: 1482775

Alternate Identifier(s):: OSTI ID: 1610395

Grant/Contract Number:: FG02-98ER20311; R35GM122560

Resource Type:: Published Article

Journal Name:: Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:: Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 49; Journal ID: ISSN 0027-8424

Publisher:: Proceedings of the National Academy of Sciences

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Muller's ratchet; genome decay; mistranslation; aminoacyl-tRNA synthetases; quality control

Citation Formats


                    Melnikov, Sergey V., van den Elzen, Antonia, Stevens, David L., Thoreen, Carson C., and Söll, Dieter. Loss of protein synthesis quality control in host-restricted organisms.  United States: N. p., 2018. 
Web.  doi:10.1073/pnas.1815992115.

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                    Melnikov, Sergey V., van den Elzen, Antonia, Stevens, David L., Thoreen, Carson C., & Söll, Dieter. Loss of protein synthesis quality control in host-restricted organisms.  United States.  https://doi.org/10.1073/pnas.1815992115

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                    Melnikov, Sergey V., van den Elzen, Antonia, Stevens, David L., Thoreen, Carson C., and Söll, Dieter. Mon .  
"Loss of protein synthesis quality control in host-restricted organisms".  United States.  https://doi.org/10.1073/pnas.1815992115.

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@article{osti_1482775,

  title        = {Loss of protein synthesis quality control in host-restricted organisms},

  author       = {Melnikov, Sergey V. and van den Elzen, Antonia and Stevens, David L. and Thoreen, Carson C. and Söll, Dieter},

  abstractNote = {Intracellular organisms, such as obligate parasites and endosymbionts, typically possess small genomes due to continuous genome decay caused by an environment with alleviated natural selection. Previously, a few species with highly reduced genomes, including the intracellular pathogens Mycoplasma and Microsporidia, have been shown to carry degenerated editing domains in aminoacyl-tRNA synthetases. These defects in the protein synthesis machinery cause inaccurate translation of the genetic code, resulting in significant statistical errors in protein sequences that are thought to help parasites to escape immune response of a host. In this study we analyzed 10,423 complete bacterial genomes to assess conservation of the editing domains in tRNA synthetases, including LeuRS, IleRS, ValRS, ThrRS, AlaRS, and PheRS. We found that, while the editing domains remain intact in free-living species, they are degenerated in the overwhelming majority of host-restricted bacteria. Our work illustrates that massive genome erosion triggered by an intracellular lifestyle eradicates one of the most fundamental components of a living cell: the system responsible for proofreading of amino acid selection for protein synthesis. Finally, this finding suggests that inaccurate translation of the genetic code might be a general phenomenon among intercellular organisms with reduced genomes.},

  doi          = {10.1073/pnas.1815992115},

  journal      = {Proceedings of the National Academy of Sciences of the United States of America},

  number       = 49,

  volume       = 115,

  place        = {United States},

  year         = {Mon Nov 19 00:00:00 EST 2018},

  month        = {Mon Nov 19 00:00:00 EST 2018}

}

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Title: Loss of protein synthesis quality control in host-restricted organisms

Abstract

Citation Formats

Molecular basis of alanine discrimination in editing site journal, August 2005

Molecular chaperones and selection against mutations journal, January 2008

Genetic code flexibility in microorganisms: novel mechanisms and impact on physiology journal, September 2015

Structural Basis for Substrate Recognition by the Editing Domain of Isoleucyl-tRNA Synthetase journal, June 2006

Universal pathway for posttransfer editing reactions: Insights from the crystal structure of Tt PheRS with puromycin journal, March 2015

Overview of the CCP 4 suite and current developments journal, March 2011

Trans-editing of mischarged tRNAs journal, December 2003

Accumulation of Deleterious Mutations in Endosymbionts: Muller’s Ratchet with Two Levels of Selection journal, October 2000

Extreme genome reduction in symbiotic bacteria journal, November 2011

Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy journal, November 2014

Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability journal, February 2003

Intracellular Protozoan Parasites of Humans: The Role of Molecular Chaperones in Development and Pathogenesis journal, February 2011

Structural Basis for Non-cognate Amino Acid Discrimination by the Valyl-tRNA Synthetase Editing Domain journal, June 2005

Enzyme Structure with Two Catalytic Sites for Double-Sieve Selection of Substrate journal, April 1998

Proteome-wide measurement of non-canonical bacterial mistranslation by quantitative mass spectrometry of protein modifications journal, July 2016

Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization journal, May 2009

Error-prone protein synthesis in parasites with the smallest eukaryotic genome journal, June 2018

Loss of Editing Activity during the Evolution of Mitochondrial Phenylalanyl-tRNA Synthetase journal, September 2005

Editing of misaminoacylated tRNA controls the sensitivity of amino acid stress responses in Saccharomyces cerevisiae journal, February 2017

Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi journal, November 2001

An Aminoacyl-tRNA Synthetase with a Defunct Editing Site † journal, March 2005

Translational fidelity and mistranslation in the cellular response to stress journal, August 2017

GroEL buffers against deleterious mutations journal, May 2002

Aminoacylation error correction journal, November 1996

Amino Acid Toxicities of Escherichia coli That Are Prevented by Leucyl-tRNA Synthetase Amino Acid Editing journal, September 2007

50 Million Years of Genomic Stasis in Endosymbiotic Bacteria journal, June 2002

The genome sequence of Rickettsia prowazekii and the origin of mitochondria journal, November 1998

Naturally occurring aminoacyl-tRNA synthetases editing-domain mutations that cause mistranslation in Mycoplasma parasites journal, May 2011

A Conserved Threonine within Escherichia coli Leucyl-tRNA Synthetase Prevents Hydrolytic Editing of Leucyl-tRNA Leu † journal, May 2001

A tipping point for mistranslation and disease journal, April 2009

A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects journal, January 2016

Global Effects of Mistranslation from an Editing Defect in Mammalian Cells journal, October 2006

Structures of Two Bacterial Prolyl-tRNA Synthetases with and without a cis-Editing Domain journal, October 2006

Mechanism of tRNA-dependent editing in translational quality control journal, December 2006

Evolution of Intracellular Pathogens journal, October 2008

Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration journal, August 2006

Organellar genes journal, July 2000

Protein mistranslation: friend or foe? journal, August 2014

Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega journal, January 2011

Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation journal, June 2013

The non‐standard genetic code of Candida spp.: an evolving genetic code or a novel mechanism for adaptation? journal, October 1997

Accelerated evolution and Muller's rachet in endosymbiotic bacteria. journal, April 1996

Enlarging the Amino Acid Set of Escherichia coli by Infiltration of the Valine Coding Pathway journal, April 2001

ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules journal, May 2016

The Tiniest Tiny Genomes journal, September 2014

Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase journal, June 2012

Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondrial Leucyl-tRNA Synthetase journal, August 2015

The relation of recombination to mutational advance journal, May 1964

Reductive evolution of resident genomes journal, July 1998

Cell-specific differences in the requirements for translation quality control journal, February 2010

Molecular basis of alanine discrimination in editing site
journal, August 2005

Molecular chaperones and selection against mutations
journal, January 2008

Genetic code flexibility in microorganisms: novel mechanisms and impact on physiology
journal, September 2015

Structural Basis for Substrate Recognition by the Editing Domain of Isoleucyl-tRNA Synthetase
journal, June 2006

Universal pathway for posttransfer editing reactions: Insights from the crystal structure of Tt PheRS with puromycin
journal, March 2015

Overview of the CCP 4 suite and current developments
journal, March 2011

Trans-editing of mischarged tRNAs
journal, December 2003

Accumulation of Deleterious Mutations in Endosymbionts: Muller’s Ratchet with Two Levels of Selection
journal, October 2000

Extreme genome reduction in symbiotic bacteria
journal, November 2011

Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy
journal, November 2014

Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability
journal, February 2003

Intracellular Protozoan Parasites of Humans: The Role of Molecular Chaperones in Development and Pathogenesis
journal, February 2011

Structural Basis for Non-cognate Amino Acid Discrimination by the Valyl-tRNA Synthetase Editing Domain
journal, June 2005

Enzyme Structure with Two Catalytic Sites for Double-Sieve Selection of Substrate
journal, April 1998

Proteome-wide measurement of non-canonical bacterial mistranslation by quantitative mass spectrometry of protein modifications
journal, July 2016

Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization
journal, May 2009

Error-prone protein synthesis in parasites with the smallest eukaryotic genome
journal, June 2018

Loss of Editing Activity during the Evolution of Mitochondrial Phenylalanyl-tRNA Synthetase
journal, September 2005

Editing of misaminoacylated tRNA controls the sensitivity of amino acid stress responses in Saccharomyces cerevisiae
journal, February 2017

Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi
journal, November 2001

An Aminoacyl-tRNA Synthetase with a Defunct Editing Site ^†
journal, March 2005

Translational fidelity and mistranslation in the cellular response to stress
journal, August 2017

GroEL buffers against deleterious mutations
journal, May 2002

Aminoacylation error correction
journal, November 1996

Amino Acid Toxicities of Escherichia coli That Are Prevented by Leucyl-tRNA Synthetase Amino Acid Editing
journal, September 2007

50 Million Years of Genomic Stasis in Endosymbiotic Bacteria
journal, June 2002

The genome sequence of Rickettsia prowazekii and the origin of mitochondria
journal, November 1998

Naturally occurring aminoacyl-tRNA synthetases editing-domain mutations that cause mistranslation in Mycoplasma parasites
journal, May 2011

A Conserved Threonine within Escherichia coli Leucyl-tRNA Synthetase Prevents Hydrolytic Editing of Leucyl-tRNA ^Leu ^†
journal, May 2001

A tipping point for mistranslation and disease
journal, April 2009

A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects
journal, January 2016

Global Effects of Mistranslation from an Editing Defect in Mammalian Cells
journal, October 2006

Structures of Two Bacterial Prolyl-tRNA Synthetases with and without a cis-Editing Domain
journal, October 2006

Mechanism of tRNA-dependent editing in translational quality control
journal, December 2006

Evolution of Intracellular Pathogens
journal, October 2008

Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration
journal, August 2006

Organellar genes
journal, July 2000

Protein mistranslation: friend or foe?
journal, August 2014

Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega
journal, January 2011

Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
journal, June 2013

The non‐standard genetic code of Candida spp.: an evolving genetic code or a novel mechanism for adaptation?
journal, October 1997

Accelerated evolution and Muller's rachet in endosymbiotic bacteria.
journal, April 1996

Enlarging the Amino Acid Set of Escherichia coli by Infiltration of the Valine Coding Pathway
journal, April 2001

ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules
journal, May 2016

The Tiniest Tiny Genomes
journal, September 2014

Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase
journal, June 2012

Degenerate Connective Polypeptide 1 (CP1) Domain from Human Mitochondrial Leucyl-tRNA Synthetase
journal, August 2015

The relation of recombination to mutational advance
journal, May 1964

Reductive evolution of resident genomes
journal, July 1998

Cell-specific differences in the requirements for translation quality control
journal, February 2010