title: Adaptations to a subterranean environment and longevity revealed by the analysis of mole rat genomes.
abstract: Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis) and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber). Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Inge
authors.initials: I
authors.lastname: Seim
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Gerashchenko
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Turanov
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Lobanov
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Fan
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yao
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Siming
authors.initials: S
authors.lastname: Ma
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Sang-Goo
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Eun Bae
authors.initials: EB
authors.lastname: Kim
authors.affiliation: Rodent Histopathology Laboratory, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.affiliation: University of South Bohemia, Faculty of Science, Ceske Budejovice 37005, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Šumbera
authors.affiliation: Department of Physiology and The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Buffenstein
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen, 2200 Copenhagen N, Denmark.
authors.forename: Guojie
authors.initials: G
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen, 2200 Copenhagen N, Denmark; King Abdulaziz University, Jeddah 21441, Saudi Arabia. Electronic address: wangj@genomics.org.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea. Electronic address: vgladyshev@rics.bwh.harvard.edu.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000199:Actins / Q000235:genetics; D000222:Adaptation, Physiological / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017753:Ecosystem; D049810:Genetic Speciation; D016678:Genome; D005914:Globins / Q000235:genetics; D007328:Insulin / Q000235:genetics; D008136:Longevity; D008550:Melatonin / Q000235:genetics; D019577:Mole Rats / Q000235:genetics*; D008969:Molecular Sequence Data; D010146:Pain / Q000235:genetics; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D022722:Thermogenesis / Q000235:genetics; D059467:Transcriptome
chemical_list: D000199:Actins; D007328:Insulin; D012339:RNA, Ribosomal, 28S; D005914:Globins; D008550:Melatonin