The features of polyglutamine regions depend on their evolutionary stability
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Pablo Mier
- Miguel A Andrade-Navarro
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000536941700001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1186/s12862-020-01626-3
- Externe Identifier
- Clarivate Analytics Document Solution ID: LT3AB
- PubMed Identifier: 32448113
- ISSN
- 1471-2148
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BMC EVOLUTIONARY BIOLOGY
- Schlüsselwörter
- Homorepeat
- polyQ
- Glutamine
- Codon usage
- Evolutionary stability
- Artikelnummer
- ARTN 59
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- The features of polyglutamine regions depend on their evolutionary stability
- Sub types
- Article
- Ausgabe der Zeitschrift
- 20
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.</jats:p> </jats:sec>
- Autoren
- Pablo Mier
- Miguel A Andrade-Navarro
- DOI
- 10.1186/s12862-020-01626-3
- eISSN
- 1471-2148
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BMC Evolutionary Biology
- Sprache
- en
- Artikelnummer
- 59
- Online publication date
- 2020
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1186/s12862-020-01626-3
- Datum der Datenerfassung
- 2021
- Titel
- The features of polyglutamine regions depend on their evolutionary stability
- Ausgabe der Zeitschrift
- 20
Datenquelle: Crossref
- Abstract
- <h4>Background</h4>Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context.<h4>Results</h4>Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ.<h4>Conclusions</h4>Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.
- Addresses
- Institute of Organismic and Molecular Evolution, Faculty of Biology, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128, Mainz, Germany. munoz@uni-mainz.de.
- Autoren
- Pablo Mier
- Miguel A Andrade-Navarro
- DOI
- 10.1186/s12862-020-01626-3
- eISSN
- 1471-2148
- Externe Identifier
- PubMed Identifier: 32448113
- PubMed Central ID: PMC7247214
- Funding acknowledgements
- H2020 Marie Skłodowska-Curie Actions: 823886
- Deutsche Forschungsgemeinschaft: AN735/4-1
- Open access
- true
- ISSN
- 1471-2148
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BMC evolutionary biology
- Schlüsselwörter
- Humans
- Peptides
- Proteome
- Protein Interaction Mapping
- Evolution, Molecular
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- 59
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- The features of polyglutamine regions depend on their evolutionary stability.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 20
Files
https://bmcecolevol.biomedcentral.com/track/pdf/10.1186/s12862-020-01626-3 https://europepmc.org/articles/PMC7247214?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- BACKGROUND: Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context. RESULTS: Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ. CONCLUSIONS: Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.
- Date of acceptance
- 2020
- Autoren
- Pablo Mier
- Miguel A Andrade-Navarro
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/32448113
- DOI
- 10.1186/s12862-020-01626-3
- eISSN
- 1471-2148
- Externe Identifier
- PubMed Central ID: PMC7247214
- Funding acknowledgements
- H2020 Marie Skłodowska-Curie Actions: 823886
- Deutsche Forschungsgemeinschaft: AN735/4-1
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BMC Evol Biol
- Schlüsselwörter
- Codon usage
- Evolutionary stability
- Glutamine
- Homorepeat
- polyQ
- Evolution, Molecular
- Humans
- Peptides
- Protein Interaction Mapping
- Proteome
- Sprache
- eng
- Country
- England
- Paginierung
- 59
- PII
- 10.1186/s12862-020-01626-3
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Titel
- The features of polyglutamine regions depend on their evolutionary stability.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 20
Datenquelle: PubMed
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