The inevitability of unconditionally deleterious substitutions during adaptation

McCandlish, D. M., Epstein, C. L., Plotkin, J. B. (May 2014) The inevitability of unconditionally deleterious substitutions during adaptation. Evolution, 68 (5). pp. 1351-64. ISSN 1558-5646 (Electronic)0014-3820 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/24410330
DOI: 10.1111/evo.12350

Abstract

Studies on the genetics of adaptation from new mutations typically neglect the possibility that a deleterious mutation might fix. Nonetheless, here we show that, in many regimes, the first mutation to fix is most often deleterious, even when fitness is expected to increase in the long term. In particular, we prove that this phenomenon occurs under weak mutation for any house-of-cards model with an equilibrium distribution. We find that the same qualitative results hold under Fisher's geometric model. We also provide a simple intuition for the surprising prevalence of unconditionally deleterious substitutions during early adaptation. Importantly, the phenomenon we describe occurs on fitness landscapes without any local maxima and is therefore distinct from "valley crossing." Our results imply that the common practice of ignoring deleterious substitutions leads to qualitatively incorrect predictions in many regimes. Our results also have implications for the substitution process at equilibrium and for the response to a sudden decrease in population size.

Item Type: Paper
Uncontrolled Keywords: Adaptation, Physiological/*genetics *Amino Acid Substitution Animals *Evolution, Molecular *Genetic Fitness *Models, Genetic Mutation Deleterious fixations Fisher's geometric model house of cards reversible Markov chain weak mutation
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
evolution
CSHL Authors:
Communities: CSHL labs > McCandlish lab
Depositing User: Matt Covey
Date: May 2014
Date Deposited: 18 Jan 2017 20:26
Last Modified: 18 Jan 2017 20:26
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34041

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