ArticleMolecular biology and evolution2019
Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression.
Article in Molecular biology and evolution, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 66 citations in OpenAlex.
- Wolves in Bhutan Are Part of the Ancient Himalayan Wolf (Ecology and evolution · 2026Article
- A Deep Dive into the Globin Superfamily of Sharks, Skates, and Rays: Contrasting Patterns of Gene Loss and Retention Relative to Bony Vertebrates.Genome biology and evolution · 2026Article
- Hemoglobin-Gene Cluster Deletions in Antarctic White-Blooded Icefishes Facilitated by Transposable Elements.Genome biology and evolution · 2025Article
- Unraveling the Mystery of Hemoglobin in Hypoxia-Accelerated Neurodegenerative Diseases.Biomolecules · 2025Review
- Integrating Intermediate Traits in Phylogenetic Genotype-to-Phenotype Studies.Integrative and comparative biology · 2025Review
- Introgression drives adaptation to the plateau environment in a subterranean rodent.BMC biology · 2024Article
- Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep.Genomics, proteomics & bioinformatics · 2024Article
- North African fox genomes show signatures of repeated introgression and adaptation to life in deserts.Nature ecology & evolution · 2023Article
- Markhor-derived Introgression of a Genomic Region Encompassing PAPSS2 Confers High-altitude Adaptability in Tibetan Goats.Molecular biology and evolution · 2022Article
- Polycythemia in dogs with chronic hypoxic pulmonary disease.Journal of veterinary internal medicine · 2022Article
- Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas.Nature ecology & evolution · 2022Article
- Altitude acclimatization, hemoglobin-oxygen affinity, and circulatory oxygen transport in hypoxia.Molecular aspects of medicine · 2022Review
- The genomic basis of high-elevation adaptation in wild house mice (Mus musculus domesticus) from South America.Genetics · 2022Article
- 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
- Genome-wide scan for selective footprints and genes related to cold tolerance in Chantecler chickens.Zoological research · 2021Article
- Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts.Molecular biology and evolution · 2021Article
- Article
- High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology.Molecular biology and evolution · 2021Review
- Evolved increases in hemoglobin-oxygen affinity and the Bohr effect coincided with the aquatic specialization of penguins.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
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Abstract
A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the β-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked β-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the β-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.
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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.