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Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty

Orthologs separate after lineages split from each other and paralogs after gene duplications. Thus, orthologs are expected to remain more functionally coherent across lineages, while paralogs have been proposed as a source of new functions. Because protein functional divergence follows from non-syno...

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Autores principales: Escorcia-Rodríguez, Juan M., Esposito, Mario, Freyre-González, Julio A., Moreno-Hagelsieb, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440661/
https://www.ncbi.nlm.nih.gov/pubmed/36065404
http://dx.doi.org/10.7717/peerj.13843
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author Escorcia-Rodríguez, Juan M.
Esposito, Mario
Freyre-González, Julio A.
Moreno-Hagelsieb, Gabriel
author_facet Escorcia-Rodríguez, Juan M.
Esposito, Mario
Freyre-González, Julio A.
Moreno-Hagelsieb, Gabriel
author_sort Escorcia-Rodríguez, Juan M.
collection PubMed
description Orthologs separate after lineages split from each other and paralogs after gene duplications. Thus, orthologs are expected to remain more functionally coherent across lineages, while paralogs have been proposed as a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS), as proxy for functional divergence. We used five working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering. The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, suggesting that orthologs generally tend to be more functionally stable than paralogs. The differences in dN/dS ratios remained suggesting the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes with high codon usage biases, low coverage of either of the aligned sequences, or sequences with very high similarities. Separation by percent identity of the encoded proteins showed that the differences between the dN/dS ratios of orthologs and paralogs were more evident at high sequence identity, less so as identity dropped. The last results suggest that the differences between dN/dS ratios were partially related to differences in protein identity. However, they also suggested that paralogs undergo functional divergence relatively early after duplication. Our analyses indicate that choosing orthologs as probably functionally coherent remains the right approach in comparative genomics.
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spelling pubmed-94406612022-09-04 Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty Escorcia-Rodríguez, Juan M. Esposito, Mario Freyre-González, Julio A. Moreno-Hagelsieb, Gabriel PeerJ Bioinformatics Orthologs separate after lineages split from each other and paralogs after gene duplications. Thus, orthologs are expected to remain more functionally coherent across lineages, while paralogs have been proposed as a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS), as proxy for functional divergence. We used five working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering. The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, suggesting that orthologs generally tend to be more functionally stable than paralogs. The differences in dN/dS ratios remained suggesting the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes with high codon usage biases, low coverage of either of the aligned sequences, or sequences with very high similarities. Separation by percent identity of the encoded proteins showed that the differences between the dN/dS ratios of orthologs and paralogs were more evident at high sequence identity, less so as identity dropped. The last results suggest that the differences between dN/dS ratios were partially related to differences in protein identity. However, they also suggested that paralogs undergo functional divergence relatively early after duplication. Our analyses indicate that choosing orthologs as probably functionally coherent remains the right approach in comparative genomics. PeerJ Inc. 2022-08-31 /pmc/articles/PMC9440661/ /pubmed/36065404 http://dx.doi.org/10.7717/peerj.13843 Text en © 2022 Escorcia-Rodríguez et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Escorcia-Rodríguez, Juan M.
Esposito, Mario
Freyre-González, Julio A.
Moreno-Hagelsieb, Gabriel
Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title_full Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title_fullStr Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title_full_unstemmed Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title_short Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
title_sort non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440661/
https://www.ncbi.nlm.nih.gov/pubmed/36065404
http://dx.doi.org/10.7717/peerj.13843
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