title: Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic.
abstract: Woolly mammoths and living elephants are characterized by major phenotypic differences that have allowed them to live in very different environments. To identify the genetic changes that underlie the suite of woolly mammoth adaptations to extreme cold, we sequenced the nuclear genome from three Asian elephants and two woolly mammoths, and we identified and functionally annotated genetic changes unique to woolly mammoths. We found that genes with mammoth-specific amino acid changes are enriched in functions related to circadian biology, skin and hair development and physiology, lipid metabolism, adipose development and physiology, and temperature sensation. Finally, we resurrected and functionally tested the mammoth and ancestral elephant TRPV3 gene, which encodes a temperature-sensitive transient receptor potential (thermoTRP) channel involved in thermal sensation and hair growth, and we show that a single mammoth-specific amino acid substitution in an otherwise highly conserved region of the TRPV3 channel strongly affects its temperature sensitivity.
authors.affiliation: Department of Human Genetics, The University of Chicago, 920 East 58th Street, CLSC 319C, Chicago, IL 60637, USA. Electronic address: vjlynch@uchicago.edu.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Lynch
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, 506B Wartik Lab, University Park, PA 16802, USA.
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Bedoya-Reina
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, 506B Wartik Lab, University Park, PA 16802, USA.
authors.forename: Aakrosh
authors.initials: A
authors.lastname: Ratan
authors.affiliation: Department of Human Genetics, The University of Chicago, 920 East 58th Street, CLSC 319C, Chicago, IL 60637, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sulak
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, 506B Wartik Lab, University Park, PA 16802, USA.
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Drautz-Moses
authors.affiliation: Departments of Anthropology and Biology, Pennsylvania State University, 513 Carpenter Building, University Park, PA 16802, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Perry
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, 506B Wartik Lab, University Park, PA 16802, USA. Electronic address: webb@bx.psu.edu.
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, 506B Wartik Lab, University Park, PA 16802, USA.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schuster
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001110:Arctic Regions; D004606:Elephants / Q000145:classification / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D016678:Genome; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056665:Mammoths / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D050916:TRPV Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels