Mutation bias shapes the spectrum of adaptive substitutions

Author:

Cano Alejandro V.12ORCID,Rozhoňová Hana12ORCID,Stoltzfus Arlin34ORCID,McCandlish David M.5,Payne Joshua L.12

Affiliation:

1. Institute of Integrative Biology, ETH Zurich, 8092 Zurich, Switzerland

2. Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland

3. Data Science Group, Office of Data and Informatics, Material Measurement Laboratory, National Institute of Standards and Technology, Rockville, MD 20899

4. Institute for Bioscience and Biotechnology Research, Rockville, MD 20850

5. Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Abstract

Significance How do mutational biases influence the process of adaptation? A common assumption is that selection alone determines the course of adaptation from abundant preexisting variation. Yet, theoretical work shows broad conditions under which the mutation rate to a given type of variant strongly influences its probability of contributing to adaptation. Here we introduce a statistical approach to analyzing how mutation shapes protein sequence adaptation. Using large datasets from three different species, we show that the mutation spectrum has a proportional influence on the types of changes fixed in adaptation. We also show via computer simulations that a variety of factors can influence how closely the spectrum of adaptive substitutions reflects the spectrum of variants introduced by mutation.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

John Templeton Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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