Molecular function limits divergent protein evolution on planetary timescales
Functional conservation is known to constrain protein evolution. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. We investigate these fundamental questions by characterizi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/39705 |
| _version_ | 1811181000448802816 |
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| author | Mariam M Konaté Germán Plata Jimin Park Dinara R Usmanova Harris Wang Dennis Vitkup |
| author_facet | Mariam M Konaté Germán Plata Jimin Park Dinara R Usmanova Harris Wang Dennis Vitkup |
| author_sort | Mariam M Konaté |
| collection | DOAJ |
| description | Functional conservation is known to constrain protein evolution. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. We investigate these fundamental questions by characterizing the divergence between ancient protein orthologs with conserved molecular function. Our results demonstrate that the decline of sequence and structural similarities between such orthologs significantly slows down after ~1–2 billion years of independent evolution. As a result, the sequence and structural similarities between ancient orthologs have not substantially decreased for the past billion years. The effective divergence limit (>25% sequence identity) is not primarily due to protein sites universally conserved in all linages. Instead, less than four amino acid types are accepted, on average, per site across orthologous protein sequences. Our analysis also reveals different divergence patterns for protein sites with experimentally determined small and large fitness effects of mutations.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). |
| first_indexed | 2024-04-11T09:12:13Z |
| format | Article |
| id | doaj.art-f05496596e4847a6ac2c657d10d65cf6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:13Z |
| publishDate | 2019-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f05496596e4847a6ac2c657d10d65cf62022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.39705Molecular function limits divergent protein evolution on planetary timescalesMariam M Konaté0Germán Plata1https://orcid.org/0000-0002-6470-7748Jimin Park2Dinara R Usmanova3https://orcid.org/0000-0001-5031-0013Harris Wang4https://orcid.org/0000-0003-2164-4318Dennis Vitkup5https://orcid.org/0000-0003-4259-8162Department of Systems Biology, Columbia University, New York, United States; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, United StatesDepartment of Systems Biology, Columbia University, New York, United StatesDepartment of Systems Biology, Columbia University, New York, United States; Department of Pathology and Cell Biology, Columbia University, New York, United StatesDepartment of Systems Biology, Columbia University, New York, United StatesDepartment of Systems Biology, Columbia University, New York, United States; Department of Pathology and Cell Biology, Columbia University, New York, United StatesDepartment of Systems Biology, Columbia University, New York, United States; Department of Biomedical Informatics, Columbia University, New York, United StatesFunctional conservation is known to constrain protein evolution. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. We investigate these fundamental questions by characterizing the divergence between ancient protein orthologs with conserved molecular function. Our results demonstrate that the decline of sequence and structural similarities between such orthologs significantly slows down after ~1–2 billion years of independent evolution. As a result, the sequence and structural similarities between ancient orthologs have not substantially decreased for the past billion years. The effective divergence limit (>25% sequence identity) is not primarily due to protein sites universally conserved in all linages. Instead, less than four amino acid types are accepted, on average, per site across orthologous protein sequences. Our analysis also reveals different divergence patterns for protein sites with experimentally determined small and large fitness effects of mutations.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).https://elifesciences.org/articles/39705orthologous proteinevolution |
| spellingShingle | Mariam M Konaté Germán Plata Jimin Park Dinara R Usmanova Harris Wang Dennis Vitkup Molecular function limits divergent protein evolution on planetary timescales eLife orthologous protein evolution |
| title | Molecular function limits divergent protein evolution on planetary timescales |
| title_full | Molecular function limits divergent protein evolution on planetary timescales |
| title_fullStr | Molecular function limits divergent protein evolution on planetary timescales |
| title_full_unstemmed | Molecular function limits divergent protein evolution on planetary timescales |
| title_short | Molecular function limits divergent protein evolution on planetary timescales |
| title_sort | molecular function limits divergent protein evolution on planetary timescales |
| topic | orthologous protein evolution |
| url | https://elifesciences.org/articles/39705 |
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