Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens

Authors

Spencer C. Galen, University of New Mexico, Albuquerque
Chandrasekhar Natarajan, University of Nebraska-LincolnFollow
Hideaki Moriyama, University of Nebraska-LincolnFollow
Roy E. Weber, Aarhus University, AarhusFollow
Angela Fago, Aarhus University
Phred M. Benham, University of Illinois, Urbana–Champaign
Andrea N. Chavez, University of New Mexico, Albuquerque
Zachary A. Cheviron, University of Illinois at Urbana-ChampaignFollow
Jay F. Storz, University of Nebraska-LincolnFollow
Christopher C. Witt, University of New MexicoFollow

Document Type

Article

Date of this Version

2015

Citation

www.pnas.org/cgi/doi/10.1073/pnas.1507300112

Comments

Copyright PNAS

Abstract

A key question in evolutionary genetics is why certain mutations or certain types of mutation make disproportionate contributions to adaptive phenotypic evolution. In principle, the preferential fixation of particular mutations could stem directly from variation in the underlying rate of mutation to function-altering alleles. However, the influence of mutation bias on the genetic architecture of phenotypic evolution is difficult to evaluate because data on rates of mutation to function-altering alleles are seldom available. Here, we report the discovery that a single point mutation at a highly mutable site in the βA-globin gene has contributed to an evolutionary change in hemoglobin (Hb) function in high-altitude Andean house wrens (Troglodytes aedon). Results of experiments on native Hb variants and engineered, recombinant Hb mutants demonstrate that a nonsynonymous mutation at a CpG dinucleotide in the β^A-globin gene is responsible for an evolved difference in Hb–O₂ affinity between high- and low-altitude house wren populations. Moreover, patterns of genomic differentiation between high- and low-altitude populations suggest that altitudinal differentiation in allele frequencies at the causal amino acid polymorphism reflects a history of spatially varying selection. The experimental results highlight the influence of mutation rate on the genetic basis of phenotypic evolution by demonstrating that a large-effect allele at a highly mutable CpG site has promoted physiological differentiation in blood O₂ transport capacity between house wren populations that are native to different elevations.