PgmNr Y485: Genetic and environmental backgrounds constrain the course of evolutionary rescue by compensatory mutations.

Authors:
Véronique Hamel; Marie Filteau; Marie-Christine Pouliot; Isabelle Gagnon-Arsenault; Alexandre K. Dubé; Christian R. Landry


Institutes
Département de Biologie, PROTEO and Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Qc, Canada.


Keyword: Human diseases/Drug Discovery

Abstract:

Deleterious mutations segregate and often fix in small populations during the course of evolution. These deleterious mutations can be compensated for by secondary mutations known as compensatory mutations. We examined if the trajectory of compensatory evolution to a strongly deleterious mutation is dependent on the environment and the genetic background in which compensatory evolution takes place. We performed an evolutionary rescue experiment in a yeast model for the Wiskott-Aldrich syndrome (mutation in LAS17) in two genetic backgrounds and two carbon sources.  We found that compensatory mutations tend to be overrepresented in the physical interaction network surrounding Las17p, showing that protein interaction partners are prime targets for compensatory mutations. In addition, we found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment and their combination. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target and the associated fitness cost varied across contexts. Overall, our results show that the course of evolution following the fixation of a deleterious allele is highly contingent on the initial conditions in which a deleterious mutation occurs.



Yeast Database Genetic Index
1. gene symbol: LAS17; systematic name: YOR181W