title: Epistasis among adaptive mutations in deer mouse hemoglobin.
abstract: Epistatic interactions between mutant sites in the same protein can exert a strong influence on pathways of molecular evolution. We performed protein engineering experiments that revealed pervasive epistasis among segregating amino acid variants that contribute to adaptive functional variation in deer mouse hemoglobin (Hb). Amino acid mutations increased or decreased Hb-O2 affinity depending on the allelic state of other sites. Structural analysis revealed that epistasis for Hb-O2 affinity and allosteric regulatory control is attributable to indirect interactions between structurally remote sites. The prevalence of sign epistasis for fitness-related biochemical phenotypes has important implications for the evolutionary dynamics of protein polymorphism in natural populations.
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Natarajan
authors.forename: Noriko
authors.initials: N
authors.lastname: Inoguchi
authors.forename: Roy E
authors.initials: RE
authors.lastname: Weber
authors.forename: Angela
authors.initials: A
authors.lastname: Fago
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000483:Alleles; D000818:Animals; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005091:Exons; D014644:Genetic Variation; D006454:Hemoglobins / Q000737:chemistry* / Q000235:genetics*; D006860:Hydrogen Bonding; D009154:Mutation; D010100:Oxygen / Q000737:chemistry; D010542:Peromyscus / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D055542:alpha-Globins / Q000737:chemistry / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: D006454:Hemoglobins; D055542:alpha-Globins; D055544:beta-Globins; D010100:Oxygen