edoc

Shared molecular targets confer resistance over short and long evolutionary timescales

Li, Jing and Vázquez-García, Ignacio and Persson, Karl and González, Asier and Yue, Jia-Xing and Barré, Benjamin and Hall, Michael N. and Long, Anthony and Warringer, Jonas and Mustonen, Ville and Liti, Gianni. (2019) Shared molecular targets confer resistance over short and long evolutionary timescales. Molecular biology and evolution, 36 (4). pp. 691-708.

[img] PDF - Published Version
Restricted to Repository staff only until 17 January 2022.

2483Kb

Official URL: https://edoc.unibas.ch/69045/

Downloads: Statistics Overview

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0737-4038
e-ISSN:1537-1719
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:17 Jul 2019 15:10
Deposited On:17 Jul 2019 15:05

Repository Staff Only: item control page