title: Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens.
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 β(A)-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.
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131; Museum of Southwestern Biology, University of New Mexico, Albuquerque, NM 87131;
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Galen
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588;
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Natarajan
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588;
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.affiliation: Department of Bioscience, Zoophysiology, Aarhus University, DK-8000 Aarhus, Denmark;
authors.forename: Roy E
authors.initials: RE
authors.lastname: Weber
authors.affiliation: Department of Bioscience, Zoophysiology, Aarhus University, DK-8000 Aarhus, Denmark;
authors.forename: Angela
authors.initials: A
authors.lastname: Fago
authors.affiliation: Department of Animal Biology, School of Integrative Biology, University of Illinois, Urbana-Champaign, IL 61801.
authors.forename: Phred M
authors.initials: PM
authors.lastname: Benham
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131; Museum of Southwestern Biology, University of New Mexico, Albuquerque, NM 87131;
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Chavez
authors.affiliation: Department of Animal Biology, School of Integrative Biology, University of Illinois, Urbana-Champaign, IL 61801.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Cheviron
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588; jstorz2@unl.edu cwitt@unm.edu.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131; Museum of Southwestern Biology, University of New Mexico, Albuquerque, NM 87131; jstorz2@unl.edu cwitt@unm.edu.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Witt
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics* / Q000502:physiology; D000531:Altitude; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006454:Hemoglobins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D059645:Mutation Rate; D010100:Oxygen / Q000378:metabolism; D010568:Peru; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020308:Songbirds / Q000235:genetics* / Q000502:physiology; D053719:Tandem Mass Spectrometry; D055544:beta-Globins / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D055544:beta-Globins; D010100:Oxygen
keywords: biochemical adaptation; hemoglobin; high altitude; hypoxia; mutation bias