Natural variants suppress mutations in hundreds of essential genes
Abstract The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-05-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202010138 |
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| author | Leopold Parts Amandine Batté Maykel Lopes Michael W Yuen Meredith Laver Bryan‐Joseph San Luis Jia‐Xing Yue Carles Pons Elise Eray Patrick Aloy Gianni Liti Jolanda van Leeuwen |
| author_facet | Leopold Parts Amandine Batté Maykel Lopes Michael W Yuen Meredith Laver Bryan‐Joseph San Luis Jia‐Xing Yue Carles Pons Elise Eray Patrick Aloy Gianni Liti Jolanda van Leeuwen |
| author_sort | Leopold Parts |
| collection | DOAJ |
| description | Abstract The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of causal genes remain largely unknown. Here, we measure the fitness effects of ~ 1,100 temperature‐sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds and map the modifiers for 19 combinations. Altogether, fitness defects for 149 of the 580 tested genes (26%) could be suppressed by genetic variation in at least one yeast strain. Suppression was generally driven by gain‐of‐function of a single, strong modifier gene, and involved both genes encoding complex or pathway partners suppressing specific temperature‐sensitive alleles, as well as general modifiers altering the effect of many alleles. The emerging frequency of suppression and range of possible mechanisms suggest that a substantial fraction of monogenic diseases could be managed by modulating other gene products. |
| format | Article |
| id | doaj-art-547226e6c7ef427cb48bed2dc376bb17 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-547226e6c7ef427cb48bed2dc376bb172025-08-20T02:35:44ZengSpringer NatureMolecular Systems Biology1744-42922021-05-0117511610.15252/msb.202010138Natural variants suppress mutations in hundreds of essential genesLeopold Parts0Amandine Batté1Maykel Lopes2Michael W Yuen3Meredith Laver4Bryan‐Joseph San Luis5Jia‐Xing Yue6Carles Pons7Elise Eray8Patrick Aloy9Gianni Liti10Jolanda van Leeuwen11Donnelly Centre for Cellular and Biomolecular Research, University of TorontoCenter for Integrative Genomics, University of LausanneCenter for Integrative Genomics, University of LausanneDonnelly Centre for Cellular and Biomolecular Research, University of TorontoDonnelly Centre for Cellular and Biomolecular Research, University of TorontoDonnelly Centre for Cellular and Biomolecular Research, University of TorontoUniversity of Côte d’Azur, CNRS, INSERM, IRCANInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and TechnologyCenter for Integrative Genomics, University of LausanneInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and TechnologyUniversity of Côte d’Azur, CNRS, INSERM, IRCANCenter for Integrative Genomics, University of LausanneAbstract The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of causal genes remain largely unknown. Here, we measure the fitness effects of ~ 1,100 temperature‐sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds and map the modifiers for 19 combinations. Altogether, fitness defects for 149 of the 580 tested genes (26%) could be suppressed by genetic variation in at least one yeast strain. Suppression was generally driven by gain‐of‐function of a single, strong modifier gene, and involved both genes encoding complex or pathway partners suppressing specific temperature‐sensitive alleles, as well as general modifiers altering the effect of many alleles. The emerging frequency of suppression and range of possible mechanisms suggest that a substantial fraction of monogenic diseases could be managed by modulating other gene products.https://doi.org/10.15252/msb.202010138compensatory evolutiongenetic interactionsgenetic modifiersgenetic suppressionnatural variation |
| spellingShingle | Leopold Parts Amandine Batté Maykel Lopes Michael W Yuen Meredith Laver Bryan‐Joseph San Luis Jia‐Xing Yue Carles Pons Elise Eray Patrick Aloy Gianni Liti Jolanda van Leeuwen Natural variants suppress mutations in hundreds of essential genes Molecular Systems Biology compensatory evolution genetic interactions genetic modifiers genetic suppression natural variation |
| title | Natural variants suppress mutations in hundreds of essential genes |
| title_full | Natural variants suppress mutations in hundreds of essential genes |
| title_fullStr | Natural variants suppress mutations in hundreds of essential genes |
| title_full_unstemmed | Natural variants suppress mutations in hundreds of essential genes |
| title_short | Natural variants suppress mutations in hundreds of essential genes |
| title_sort | natural variants suppress mutations in hundreds of essential genes |
| topic | compensatory evolution genetic interactions genetic modifiers genetic suppression natural variation |
| url | https://doi.org/10.15252/msb.202010138 |
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