ArticleScience (New York, N.Y.)2013
Epistasis among adaptive mutations in deer mouse hemoglobin.
Article in Science (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
129 citing papers in PubMed, 205 citations in OpenAlex.
- Mechanisms of Phenotypic Evolution from Molecules to Organisms: Integrating Evolutionary Biochemistry and Evolutionary Developmental Biology.Annual review of ecology, evolution, and systematics · 2026Article
- A novel, fig-associated microbe promotes reproductive success via variable life history mechanisms inbioRxiv : the preprint server for biology · 2025Article
- Physiological Differences Underlying Divergent Hypoxia Responses and Altitude Adaptations in Humans, Rats and Mice.Comprehensive Physiology · 2025Review
- Widespread epistasis shapes RNA polymerase II active site function and evolution.Nature communications · 2025Article
- Geographic Variation in Epigenetic Responses to Hypoxia in Deer Mice (Peromyscus maniculatus) Distributed Along an Elevational Gradient.Molecular ecology · 2025Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.Nature communications · 2025Article
- Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
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- Higher-order epistasis within Pol II trigger loop haplotypes.bioRxiv : the preprint server for biology · 2024Article
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Convergent High OAnimals : an open access journal from MDPI · 2024Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.bioRxiv : the preprint server for biology · 2024Article
- The Mutational Road not Taken: Using Ancestral Sequence Resurrection to Evaluate the Evolution of Plant Enzyme Substrate Preferences.Genome biology and evolution · 2024Article
- Hypoxia Inducible Factor pathway proteins in high-altitude mammals.Trends in biochemical sciences · 2024Review
- Not Quite Lost in Translation: Mistranslation Alters Adaptive Landscape Topography and the Dynamics of Evolution.Molecular biology and evolution · 2023Article
- Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin.Current biology : CB · 2023Article
- Exploring the expanse between theoretical questions and experimental approaches in the modern study of evolvability.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Article
- Evolution in reproductive tempo and investment across the Peromyscus radiation.Journal of experimental zoology. Part A, Ecological and integrative physiology · 2023Review
- Contingency and Entrenchment of Drug-Resistance Mutations in HIV Viral Proteins.The journal of physical chemistry. B · 2022Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.