Shared molecular targets confer resistance over short and long evolutionary timescales Journal Article
| Authors: | Li, J.; Vázquez-García, I.; Persson, K.; González, A.; Yue, J. X.; Barré, B.; Hall, M. N.; Long, A.; Warringer, J.; Mustonen, V.; Liti, G. |
| Article Title: | Shared molecular targets confer resistance over short and long evolutionary timescales |
| Abstract: | Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin, respectively. The causative pre-existing and de novo variants were selected on shared targets: RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. Interestingly, the pre-existing and de novo TOR variants map to different functional domains and act via distinct mechanisms. The pre-existing TOR variants from two domesticated strains exhibited opposite rapamycin resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how pre-existing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving populations. © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
| Keywords: | drug resistance; budding yeast; adaptation; de novo mutation; pre-existing genetic variation |
| Journal Title: | Molecular Biology and Evolution |
| Volume: | 36 |
| Issue: | 4 |
| ISSN: | 0737-4038 |
| Publisher: | Oxford University Press |
| Date Published: | 2019-04-01 |
| Start Page: | 691 |
| End Page: | 708 |
| Language: | English |
| DOI: | 10.1093/molbev/msz006 |
| PUBMED: | 30657986 |
| PROVIDER: | scopus |
| PMCID: | PMC6445301 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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