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Epistasis among adaptive mutations in deer mouse hemoglobin.
Chandrasekhar Natarajan1, Noriko Inoguchi, Roy E Weber
1School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.
Science (New York, N.Y.)
|June 15, 2013
Summary
Epistasis, interactions between genetic variants, significantly impacts protein evolution. These interactions in deer mouse hemoglobin (Hb) affect oxygen binding, demonstrating complex evolutionary pathways.
Area of Science:
- Biochemistry
- Molecular Evolution
- Structural Biology
Background:
- Epistatic interactions between mutations within a protein can influence molecular evolution.
- Understanding these interactions is crucial for deciphering adaptive protein variation.
Purpose of the Study:
- To investigate pervasive epistasis among amino acid variants in deer mouse hemoglobin (Hb).
- To determine how these epistatic interactions affect Hb-O2 affinity and allosteric regulation.
Main Methods:
- Performed protein engineering experiments on deer mouse hemoglobin.
- Conducted structural analysis to understand the mechanisms of epistasis.
Main Results:
- Revealed pervasive epistasis among segregating amino acid variants in Hb.
- Observed that amino acid mutations altered Hb-O2 affinity based on the allelic state of other sites.
- Identified indirect interactions between structurally remote sites as the cause of epistasis for O2 affinity and allosteric control.
Conclusions:
- Epistatic interactions are prevalent in adaptive protein variation.
- Sign epistasis for biochemical phenotypes has significant implications for protein polymorphism dynamics in natural populations.
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