ArticlePLoS genetics2018
Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 77 citations in OpenAlex.
- Global Environmental Factors Impact the Evolution of Adult Hemoglobins in Squamata Reptiles (Lizards and Snakes) and Terrestrial Turtles.Genome biology and evolution · 2025Article
- Gas exchange, oxygen transport and metabolism in high-altitude waterfowl.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Physiological and Genetic Basis of High-Altitude Indigenous Animals' Adaptation to Hypoxic Environments.Animals : an open access journal from MDPI · 2024Review
- The unique allosteric property of crocodilian haemoglobin elucidated by cryo-EM.Nature communications · 2024Article
- Molecular Insights of an Avian Species with Low Oxygen Affinity, the Crystal Structure of Duck T-State Methemoglobin.The protein journal · 2024Article
- Convergent High OAnimals : an open access journal from MDPI · 2024Article
- Robust genetic codes enhance protein evolvability.PLoS biology · 2024Article
- Vesicle-enriched secretomes alter bacterial competitive abilities and are drivers of evolution in microbial communities.FEMS microbiology ecology · 2023Article
- Autumn migration of black-necked crane (Ecology and evolution · 2023Article
- Migratory songbirds exhibit seasonal modulation of the oxygen cascade.The Journal of experimental biology · 2023Article
- Exercise and Experiments of Nature.Comprehensive Physiology · 2023Article
- Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin.Current biology : CB · 2023Article
- Atomic-Level View of the Functional Transition in Vertebrate Hemoglobins: The Case of Antarctic Fish Hbs.Journal of chemical information and modeling · 2022Article
- Altitude acclimatization, hemoglobin-oxygen affinity, and circulatory oxygen transport in hypoxia.Molecular aspects of medicine · 2022Review
- Genetic variation in haemoglobin is associated with evolved changes in breathing in high-altitude deer mice.The Journal of experimental biology · 2022Article
- Time Domains of Hypoxia Responses and -Omics Insights.Frontiers in physiology · 2022Review
- Changes in hemoglobin function and isoform expression during embryonic development in the American alligator,American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Comparison of hematological traits and oxygenation properties of hemoglobins from highland and lowland Asiatic toad (Bufo gargarizans).Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2021Review
- New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin.The Journal of experimental biology · 2021Article
- High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology.Molecular biology and evolution · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
During the adaptive evolution of a particular trait, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation to adaptive phenotypic evolution depends on the form and prevalence of mutational pleiotropy. To investigate the nature of adaptive substitutions and their pleiotropic effects, we used a protein engineering approach to characterize the molecular basis of hemoglobin (Hb) adaptation in the high-flying bar-headed goose (Anser indicus), a hypoxia-tolerant species renowned for its trans-Himalayan migratory flights. To test the effects of observed substitutions on evolutionarily relevant genetic backgrounds, we synthesized all possible genotypic intermediates in the line of descent connecting the wildtype bar-headed goose genotype with the most recent common ancestor of bar-headed goose and its lowland relatives. Site-directed mutagenesis experiments revealed one major-effect mutation that significantly increased Hb-O2 affinity on all possible genetic backgrounds. Two other mutations exhibited smaller average effect sizes and less additivity across backgrounds. One of the latter mutations produced a concomitant increase in the autoxidation rate, a deleterious side-effect that was fully compensated by a second-site mutation at a spatially proximal residue. The experiments revealed three key insights: (i) subtle, localized structural changes can produce large functional effects; (ii) relative effect sizes of function-altering mutations may depend on the sequential order in which they occur; and (iii) compensation of deleterious pleiotropic effects may play an important role in the adaptive evolution of protein function.
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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.