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Shared Molecular Targets Confer Resistance over Short and Long Evolutionary Timescales

Artikel i vetenskaplig tidskrift
Författare J. Li
I. Vázquez-García
Karl O. Persson
A. González
J. X. Yue
B. Barré
M. N. Hall
A. Long
Jonas Warringer
V. Mustonen
G. Liti
Publicerad i Molecular biology and evolution
Volym 36
Nummer/häfte 4
Sidor 691-708
ISSN 1537-1719
Publiceringsår 2019
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 691-708
Språk en
Länkar dx.doi.org/10.1093/molbev/msz006
Ämnesord adaptation, budding yeast, de novo mutation, drug resistance, pre-existing genetic variation
Ämneskategorier Evolutionsbiologi, Biokemi och molekylärbiologi

Sammanfattning

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.

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