title: The molecular basis of high-altitude adaptation in deer mice.
abstract: Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus alpha-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated alpha-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity.
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America. jstorz2@unl.edu
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sabatino
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
authors.forename: Eben J
authors.initials: EJ
authors.lastname: Gering
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Nuno
authors.initials: N
authors.lastname: Ferrand
authors.forename: Bruno
authors.initials: B
authors.lastname: Monteiro
authors.forename: Michael W
authors.initials: MW
authors.lastname: Nachman
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000531:Altitude; D000595:Amino Acid Sequence; D000818:Animals; D003120:Colorado; D005785:Gene Conversion; D005787:Gene Frequency; D049810:Genetic Speciation; D005914:Globins / Q000235:genetics; D007615:Kansas; D015810:Linkage Disequilibrium; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010542:Peromyscus / Q000235:genetics* / Q000502:physiology*; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D005914:Globins