title: Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.
abstract: Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, , Kunming 650223, China, University of the Chinese Academy of Sciences, , Beijing 100039, China, Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, , Xining 810008, China, Centre for Biodiversity and Conservation Biology, Royal Ontario Museum, , Toronto, Canada , M5S 2C6.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Tong-Zuo
authors.initials: TZ
authors.lastname: Zhang
authors.forename: Gong-Hua
authors.initials: GH
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Huang
authors.forename: Xue-Long
authors.initials: XL
authors.lastname: Jiang
authors.forename: Robert W
authors.initials: RW
authors.lastname: Murphy
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
mesh_terms: D000143:Acids / Q000378:metabolism*; D000220:Adaptation, Biological / Q000502:physiology*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D006605:Hibernation / Q000502:physiology*; D008322:Mammals / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D000143:Acids; D062556:NAV1.7 Voltage-Gated Sodium Channel
keywords: SCN9A; acid insensitivity; adaptation; convergent evolution