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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 one's genetic and environmental make-ups. 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.

SUBMITTER: Filteau M

PROVIDER: S-EPMC4631203 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds.

Filteau Marie M Hamel Véronique V Pouliot Marie-Christine MC Gagnon-Arsenault Isabelle I Dubé Alexandre K AK Landry Christian R CR

Molecular systems biology 20151012 10

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 make-ups. 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 mu ...[more]

PMID: 26459777

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Project description:Understanding the extent to which ecological divergence is repeatable is essential for predicting responses of biodiversity to environmental change. Here we test the predictability of evolution, from genotype to phenotype, by studying parallel evolution in a salmonid fish, Arctic charr (Salvelinus alpinus), across eleven replicate sympatric ecotype pairs (benthivorous-planktivorous and planktivorous-piscivorous) and two evolutionary lineages. We found considerable variability in eco-morphological divergence, with several traits related to foraging (eye diameter, pectoral fin length) being highly parallel even across lineages. This suggests repeated and predictable adaptation to environment. Consistent with ancestral genetic variation, hundreds of loci were associated with ecotype divergence within lineages of which eight were shared across lineages. This shared genetic variation was maintained despite variation in evolutionary histories, ranging from postglacial divergence in sympatry (ca. 10-15kya) to pre-glacial divergence (ca. 20-40kya) with postglacial secondary contact. Transcriptome-wide gene expression (44,102 genes) was highly parallel across replicates, involved biological processes characteristic of ecotype morphology and physiology, and revealed parallelism at the level of regulatory networks. This expression divergence was not only plastic but in part genetically controlled by parallel cis-eQTL. Lastly, we found that the magnitude of phenotypic divergence was largely correlated with the genetic differentiation and gene expression divergence. In contrast, the direction of phenotypic change was mostly determined by the interplay of adaptive genetic variation, gene expression, and ecosystem size. Ecosystem size further explained variation in putatively adaptive, ecotype-associated genomic patterns within and across lineages, highlighting the role of environmental variation and stochasticity in parallel evolution. Together, our findings demonstrate the parallel evolution of eco-morphology and gene expression within and across evolutionary lineages, which is controlled by the interplay of environmental stochasticity and evolutionary contingencies, largely overcoming variable evolutionary histories and genomic backgrounds.

Dataset Information

Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds.

Publications

Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds.

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