Epistasis among adaptive mutations in deer mouse hemoglobin

Chandrasekhar Natarajan, Noriko Inoguchi, Roy E. Weber, Angela Fago, Hideaki Moriyama, Jay F. Storz

Research output: Contribution to journalArticlepeer-review

141 Scopus citations


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-O 2 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.

Original languageEnglish (US)
Pages (from-to)1324-1327
Number of pages4
Issue number6138
StatePublished - 2013

ASJC Scopus subject areas

  • General


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