Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds
Abstract Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-10-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20156444 |
| _version_ | 1797225443230744576 |
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| author | Marie Filteau Véronique Hamel Marie‐Christine Pouliot Isabelle Gagnon‐Arsenault Alexandre K Dubé Christian R Landry |
| author_facet | Marie Filteau Véronique Hamel Marie‐Christine Pouliot Isabelle Gagnon‐Arsenault Alexandre K Dubé Christian R Landry |
| author_sort | Marie Filteau |
| collection | DOAJ |
| description | Abstract Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks. |
| first_indexed | 2024-03-13T03:11:13Z |
| format | Article |
| id | doaj.art-c18131d7ad994c36ad914cf2bdbf9379 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-04-24T14:09:05Z |
| publishDate | 2015-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-c18131d7ad994c36ad914cf2bdbf93792024-04-03T09:38:22ZengSpringer NatureMolecular Systems Biology1744-42922015-10-011110n/an/a10.15252/msb.20156444Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgroundsMarie Filteau0Véronique Hamel1Marie‐Christine Pouliot2Isabelle Gagnon‐Arsenault3Alexandre K Dubé4Christian R Landry5Département de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaDépartement de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaDépartement de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaDépartement de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaDépartement de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaDépartement de Biologie PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Qc CanadaAbstract Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks.https://doi.org/10.15252/msb.20156444aneuploidyepistasisexperimental evolutiongenotype‐by‐environment interactionWiskott–Aldrich syndrome |
| spellingShingle | Marie Filteau Véronique Hamel Marie‐Christine Pouliot Isabelle Gagnon‐Arsenault Alexandre K Dubé Christian R Landry Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds Molecular Systems Biology aneuploidy epistasis experimental evolution genotype‐by‐environment interaction Wiskott–Aldrich syndrome |
| title | Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| title_full | Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| title_fullStr | Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| title_full_unstemmed | Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| title_short | Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| title_sort | evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds |
| topic | aneuploidy epistasis experimental evolution genotype‐by‐environment interaction Wiskott–Aldrich syndrome |
| url | https://doi.org/10.15252/msb.20156444 |
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