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Empirical study of the evolution of human cold adaptation by combining genetics and physiology

Research Project

Project/Area Number 18H02515
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 45050:Physical anthropology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Nakayama Kazuhiro  東京大学, 大学院新領域創成科学研究科, 准教授 (90433581)

Co-Investigator(Kenkyū-buntansha) 岩本 禎彦  自治医科大学, 医学部, 教授 (10232711)
斉藤 昌之  北海道大学, 獣医学研究院, 名誉教授 (80036441)
西村 貴孝  九州大学, 芸術工学研究院, 講師 (80713148)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsヒト / 寒冷適応進化 / 褐色脂肪組織 / 自然選択 / ゲノム多型 / 褐色脂肪細胞 / 熱産生 / ゲノム多様性 / 寒冷適応 / ゲノム / SNP / 遺伝学 / 生理学 / 一塩基多型 / 進化
Outline of Final Research Achievements

In order to find evidence of genetic adaptation of humans to cold environments at high latitudes, we analyzed the individual differences in brown adipose tissue, which plays an important role in human thermoregulation, and changes in thermoregulatory function under cold stimulation in detail using physiological methods, and analyzed the evolutionary patterns of genomic polymorphisms related to these differences. As a result, we were able to identify several genomic regions that may be evidence of cold adaptation during the human expansion from North Asia to the Americas.

Academic Significance and Societal Importance of the Research Achievements

ヒトは、他の霊長類と同様に、低緯度の気温が高い地域で長く進化してきた生物だが、およそ10万年前以降の氷河期に高緯度の寒冷な地域にへの進出を果たした寒さに遺伝的に適応することが、高緯度地域への進出を後押ししたと考えられているが、その実体となる遺伝子は未だに明らかになっていない。この研究では、進化遺伝学解析、遺伝医学解析、生理学解析などの異なる研究手法を組み合わせてこの課題に挑戦し、ヒトの寒冷環境への適応に寄与する有力な候補遺伝子を同定することができた。また、このような遺伝子は、現代人の肥満のしやすさなどにも関わっていると予想されるので、新たな肥満予防・治療戦略の開発にも貢献できる可能性がある。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results)

  • [Journal Article] ILDR2 stabilization is regulated by its interaction with GRP782021

    • Author(s)
      Watanabe Kazuhisa、Nakayama Kazuhiro、Ohta Satoshi、Matsumoto Ayumi、Tsuda Hidetoshi、Iwamoto Sadahiko
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 8414-8414

    • DOI

      10.1038/s41598-021-87884-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遺伝子対応栄養指導を用いた閉経後女性の肥満度および骨密度の変化.2021

    • Author(s)
      不老美也子・蒲池桂子・田中明・吉澤剛士・中山一大・香川靖雄
    • Journal Title

      日本病態栄養学会誌

      Volume: 24 Pages: 161-172

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants.2020

    • Author(s)
      Nita R, Kawabata T, Kagawa Y, Nakayama K, Yanagisawa Y, Iwamoto S, Kimura F, Miyazawa T, Tatsuta N, Arima T, Yaegashi N, Nakai K.
    • Journal Title

      Prostaglandins, Leukotrienes and Essential Fatty Acids

      Volume: 152 Pages: 102031-102031

    • DOI

      10.1016/j.plefa.2019.102031

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kbtbd11 contributes to adipocyte homeostasis through the activation of upstream stimulatory factor 1.2019

    • Author(s)
      Watanabe K, Yokota K, Yoshida K, Matsumoto A, Iwamoto S
    • Journal Title

      Heliyon

      Volume: 5 Issue: 11 Pages: e02777-e02777

    • DOI

      10.1016/j.heliyon.2019.e02777

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel upstream transcription factor 1 target gene N4bp2l1 that regulates adipogenesis.2019

    • Author(s)
      Watanabe K, Yokota K, Yoshida K, Matsumoto A, Iwamoto S
    • Journal Title

      Biochem Biophys Rep.

      Volume: 20 Pages: 100676-100676

    • DOI

      10.1016/j.bbrep.2019.100676

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kbtbd11 gene expression in adipose tissue increases in response to feeding and affects adipocyte differentiation2019

    • Author(s)
      Watanabe Kazuhisa、Yoshida Ken、Iwamoto Sadahiko
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 印刷中 Issue: 4 Pages: 925-932

    • DOI

      10.1111/jdi.12995

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applicability of supraclavicular oxygenated and total hemoglobin evaluated by near-infrared time-resolved spectroscopy as indicators of brown adipose tissue density in humans2019

    • Author(s)
      Nirengi Shinsuke、Fuse Sayuri、Amagasa Shiho、Homma Toshiyuki、Kime Ryotaro、Kuroiwa Miyuki、Endo Tasuki、Sakane Naoki、Matsushita Mami、Saito Masayuki、Kurosawa Yuko、Hamaoka Takafumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 9 Pages: 2214-2214

    • DOI

      10.3390/ijms20092214

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of circulating exosomal miR-122 levels with BAT activity in healthy humans2019

    • Author(s)
      Okamatsu-Ogura Yuko、Matsushita Mami、Bariuan Jussiaea Valente、Nagaya Kazuki、Tsubota Ayumi、Saito Masayuki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13243-13243

    • DOI

      10.1038/s41598-019-49754-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BCAA catabolism in brown fat controls energy homeostasis through SLC25A442019

    • Author(s)
      Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White P J, McGarrah R W, Ilkayeva O R, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M, Ishikawa T, Kim K, Chen Y, Sponton C H, Pradhan R N, Majd H, Greiner V J, Yoneshiro M, Brown Z, Chondronikola M, Takahashi H, Goto T, et al
    • Journal Title

      Nature

      Volume: 572 Issue: 7771 Pages: 614-619

    • DOI

      10.1038/s41586-019-1503-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic variants influencing obesity-related traits in Japanese population.2019

    • Author(s)
      Nakayama K, Inaba Y
    • Journal Title

      Annals of Human Biology

      Volume: 46 Issue: 4 Pages: 298-304

    • DOI

      10.1080/03014460.2019.1644373

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] THE RELATIONSHIP BETWEEN HUMAN COLD ADAPTATION AND UCP1 GENOTYPE.2019

    • Author(s)
      西村 貴孝
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 24 Issue: 2 Pages: 81-85

    • DOI

      10.20718/jjpa.24.2_81

    • NAID

      130007677030

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GENETICS AND ADAPTATION2018

    • Author(s)
      中山一大
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 23 Issue: 4 Pages: 189-191

    • DOI

      10.20718/jjpa.23.4_189

    • NAID

      130007580267

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range2018

    • Author(s)
      Fuse Sayuri、Nirengi Shinsuke、Amagasa Shiho、Homma Toshiyuki、Kime Ryotaro、Endo Tasuki、Sakane Naoki、Matsushita Mami、Saito Masayuki、Yoneshiro Takeshi、Kurosawa Yuko、Hamaoka Takafumi
    • Journal Title

      Journal of Biomedical Optics

      Volume: 23 Issue: 6 Pages: 1-1

    • DOI

      10.1117/1.jbo.23.6.065002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Translational Aspects of Brown Fat Activation by Food-Derived Stimulants2018

    • Author(s)
      Yoneshiro Takeshi、Matsushita Mami、Saito Masayuki
    • Journal Title

      Handbook of Experimental Pharmacology

      Volume: 251 Pages: 359-379

    • DOI

      10.1007/164_2018_159

    • ISBN
      9783030105129, 9783030105136
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ADAPTATION TO THERMAL ENVIRONMENT – LIFESTYLE MODIFICATION AFFECTING HUMAN ADAPTABILITY TO THERMAL ENVIRONMENT –2018

    • Author(s)
      若林 斉、前田 享史、西村 貴孝
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 23 Issue: 4 Pages: 167-170

    • DOI

      10.20718/jjpa.23.4_167

    • NAID

      130007580264

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトの環境適応と生活習慣病.2022

    • Author(s)
      中山一大
    • Organizer
      第15回日本がん検診・診断学会習熟講習会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Recent advances in understanding human genetic adaptation to cold environments.2021

    • Author(s)
      Nakayma K
    • Organizer
      The 2nd AsiaEvo Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病気へのかかりやすさと環境適応.2021

    • Author(s)
      中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 牧畜民における食への遺伝的適応.2021

    • Author(s)
      中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Diversity in genetic susceptibility of myopia in Europeans.2021

    • Author(s)
      Xia Tiang・中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] モンゴル人の脂質異常症抵抗性は遺伝的か?Polygenic risk score を用いた検証.2021

    • Author(s)
      胡琦・岩本禎彦・中山一大
    • Organizer
      第82回日本生理人類学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Changes In Blood Component And DNA Methylation Patterns In Healthy Men Exposed Hypobaric Hypoxia2019

    • Author(s)
      Motoi M, Toyoshima H, Nakayama K, Kishida F, Shin S, Nishimura T, Yasukouchi Y, Katsumura T, Oota H, Maeda T, Watanuki S
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Individual and sex differences of percutaneous arterial oxygen saturation (SpO2) in Bolivian people "2019

    • Author(s)
      Nishimura T, Ohnishi M, Nishihara M, Ugarute J, Yasukochi Y, Fukuda H, Watanuki S, Aoyagi K
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genome wide scanning for loci influencing brown adipose tissue activity in Japanese adults.2019

    • Author(s)
      Nakayama K
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Local Adaptation and Susceptibility to Lifestyle-related Diseases in East Asia.2019

    • Author(s)
      Nakayama K
    • Organizer
      Crossing Boundaries
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Detecting signatures of polygenic selection in East Asians2018

    • Author(s)
      Kazuhiro Nakayama
    • Organizer
      SMBE2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトの表現型とエピゲノムの多様性2018

    • Author(s)
      中山一大
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトの寒冷適応とUCP1遺伝子多型との関連2018

    • Author(s)
      西村 貴孝
    • Organizer
      日本生理人類学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Human cold adaptation and importance of UCP1 genotype to non-shivering thermogenesis2018

    • Author(s)
      Takayuki Nishimura
    • Organizer
      Physiological Anthropology and Human Ecology: Studies in Modern and Ancient Populations
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on multiple organs coordination for non-shivering thermogenesis and vasomotor control in mild cold environment in human2018

    • Author(s)
      Kentaro Matsumoto, Yusuke Kobori, Hitoshi Wakabayashi, Mami Matsushita, Toshimitsu Kameya, Takafumi Maeda, Masayuki Saito
    • Organizer
      7th International Conference on the Physiology and Pharmacology of Temperature Regulation
    • Related Report
      2018 Annual Research Report
  • [Presentation] Supraclavicular tissue total hemoglobin determined by near-infrared time-resolved spectroscopy as indicators of brown adipose tissue characteristics in humans2018

    • Author(s)
      Takafumi Hamaoka, Shinsuke Nirengi, Sayuri Fuse, Shiho Amagasa, Toshiyuki Homma, Ryotaro Kime, Miyuki Kuroiwa, Tasuki Endo, Naoki Sakane, Mami Matsushita, Masayuki Saito, Takeshi Yoneshiro, Yuko Kurosawa
    • Organizer
      International Symposium: Role of Brown Adipose Tissue in Human Health
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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