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The origin and evolution of major histocompatibility complex (MHC).

Research Project

Project/Area Number 05044127
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionThe Graduate University for Advanced Studies

Principal Investigator

TAKAHATA Naoyuki  Coordination Center for Research and Education, 教育研究交流センター, 教授 (30124217)

Co-Investigator(Kenkyū-buntansha) O'HUIGIN Colm  Max-Planck-Institut fur Biologie, Abteilung Immunogenetik Corrennstr., ブランク研究所・免疫遺伝, 助教授
UYENOYAMA M.  デューク大学, 動物教室, 教授
SATTA Yoko  Max-Planck-Institut fur Biologie, Abteilung Immunogenetik Corrennstr., ブランク研究所・免疫遺伝, 研究員
KLEIN Jan  Max-Planck-Institut fur Biologie, Abteilung Immunogenetik Corrennstr., ブランク研究所・免疫遺伝, 所長
NEI Masatoshi  Department of Biology and Institute of Molecular Evolutionary Genetics, Pennsylv, 分子進化遺伝研究所, 所長
UENOYAMA Marcy k.  Department of Zoology, Duke University, U.S.A.
COLM O'hUigi  マックス, プランク研究所・免疫遺伝, 研究員
MARCY K Uyen  デューク大学, 動物教室, 教授
MASATOSHI Ne  ペンシルバニア州立大学, 分子進化遺伝研究所, 所長
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsMhc / T-cell repertoire / Self-nonself discrimination / Mhc restriction / Diversity / Adaptive evolution / DNA sequences / Natural selection / データ解析
Research Abstract

The major histocompatibility complex (Mhc) contains a family of genes whose products play crucial roles in self and nonself discrimination. Self is one's own peptides that bind to Mhc molecules and restrict the T-cell repertoire in the thymus, whereas nonself is processed peptides of foreign antigens that can be presented in the context of Mhc molecules and trigger the immune response. Since the immune system thus controlled by Mhc molecules affects the survival of individuals, the dual function of Mhc itself must be subjected to natural selection. This international scientific research program has focused on (1) DNA sequence analysis and population genetics theory on the origin and evolution of Mhc molecules and (2) the origin of mankind from a viewpoint of the Mhc diversity.
(1) The origin and evolution of Mhc molecules : Although a number of attempts were made to isolate Mhc genes from jawless fishes and lower vertebrates, all were unsuccessful. This indicates that Mhc evolved at the … More early evolutionary stage of vertebrates. Since the vertebrate immune system involves Ig and T cell receptor genes, the molecular mechanism of genomic rearrangement was also acquired around the same time as the emergence of Mhc. We have argued why the immune system and the vertebrate evolution emerged in parallel in terms of the complexity of body and the number of offspring. Natural selection for Mhc genes is intimately related to the dual function of Mhc Molecules and selection is responsible for an extraordinary diversity of Mhc molecules within a species. We have estimated the intensity of natural selection operating on Mhc molecules, and based on this estimate, we plan to develop a conservation program for endangered species. The agent of natural selection is parasites : These and Mhc variants have been coevolving. Different parasites in different geographic regions are in part a cause of human Mhc (HLA) differentiation. Recent change in our society and improvement of environment suggest relaxation of natural selection for Mhc or loss of the diversity, thus posing a serious question on the defense system in the future mankind.
(2) Diversity and local differentiation of human Mhc (HLA). Local differentiation of HLA is a reflection of local selection owing to different parasites as well as migration routes in the past. Conversely, the current HLA distribution allows us to infer migration routes of our ancestors. We have proposed a method in searching for vanished migration routes with special reference to recombination fraction. This method allows us to estimate when and among which populations migrations occurred : The higher the recombination fraction, the more recent migration event.
Finally we have studied the origin of self-incompatibility in plants because the theoretical basis is similar to that for Mhc. We have pointed out that the emergence of selfincompatibility system coincided with the emergence of flowering plants, and will further investigate why. Less

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Takahata,N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Satta,Y.: "Intensity of natural selection at the major histocompatibility complex loci." Proc.Natl.Acad.Sci.USA. 91. 7180-7188 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "Repeated failures that led to the eventual success in human evolution." Mol.Biol.Evol.11. 803-805 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "Divergence time and population size in the lineage leading to modern humans." Theor.Popul.Biol.(in press).(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "NHC diversity and selection" Immunological Review.(in press).(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "A genetic perspective on the origin and history of humans." Annual Review of Ecology and Systematics. (in press).(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "The Neutral Theory of Molecular Evolution. In Principles of Medical Biology,Vol.1B,Bioethics,eds by E.E.Bittar and N.Bittar." JAI Press Inc.Connecticut, 30 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.(eds.): "Motoo Kimura.Selected Papers on Population Genetics and Molecular Evolution." The Chicago University Press., 686 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata,N.: "Polymorphism at MHC loci and isolation by the immune system in vertebrates.(ed.Brian Golding) in Non-neutral Evolution:Theories and Molecular Data" Chapman & Hall, 20 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Klein,J.: "Whence do we come? Human origin in the light of molecular genetics." Cambridge University Press (in press), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Satta, Y.: "Intensity of Natural Selection at the Major histocompatibility complex loci." Proc.Natl.Acad.Sci.USA. 91. 7184-7188 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: "Repeated failures that led to the eventual success in human evolution." Mol.Biol.Evol.11. 803-805 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: "Divergence time and population size in the lineage leading to modern humans." Theor.Popul.Biol.(in press).(1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: "MHC diversity and selection." Immunological Review.(in press).(1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: "A genetic perspective on the origin and history of humans." Annual Review of Ecology and Systematics. (in press).(1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: JAI Press Inc.Connecticut. The Neutral Theory of Molecular Evolution. In Principles of Medical Biology, Vol.1B,Bioethics, eds by E.E.Bittar and N.Bittar., 203-232 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.(eds.): The Chicago University Press.Motoo Kimura.Selected Papers on Population Genetics and Molecular Evolution., 1-686 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahata, N.: Chapman & Hall. Polymorphism at MHC loci and isolation by the immune system in vertebrates. (ed.Brian Golding) in Non-neutral Evolution : Theories and Molecular Data, 233-252 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Klein, J.: Cambridge University Press (in press). Whence do we come? Human origin in the light of molecular genetics., (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Klein,J.: "The molecular descent of the major histocompatibility complex." Ann.Rev.Immuno.11. 269-295 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N.: "Allelic genealogy and human evolution." Mol.Biol.Evol.10. 2-22 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nei,M: "Effective population size,nucleotide diversity,and coalescence time in subdivided populations." J.Mol.Evol.37. 240-244 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kondo,R.: "Evolution of hominoid mitochondrial DNA with special reference to the silent substitution rate over the genome." J.Mol.Evol.36. 517-531 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Satta,Y.: "The synonymous substitution rate at the major histocompatibility complex loci(Mhc)in primates." Proc.Natl.Acad.Sci.USA. 90. 7480-7484 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Klein,J.: "Mhc polymorphism and human origins." Sci.Amer.269. 46-51 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Klein,J.: "Trans-specific Mhc polymorphism and the origin of species." J.Med.Primatol.22. 57-64 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N.: "Introductory comments on major papers by Professor Motoo Kimura." Jnp.J.Genet.68. 353-395 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N.: "Relaxed natural selection in human populations during the Pleistocene." Jpn.J.Genet.68. 539-547 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N. (eds.Takahata,N.& A.G.Clark): "Mechanisms of Molecular Evolution." Japan Sci.Soc.Press,Tokyo/Sinauer Associates,Sunderland,MA., 250 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N. (eds.J.Gergely,et al): "Trans-species polumorphism at the major histocompatibility complex loci.In Progress in Immunology VIII." Springer/Verlag., 153-158 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,N. (ed.Partha P.Majumder): "Haldanes'contribution to the understanding of the evolution of vertebrate immune system.In Human Population Genetics:A centennial tribute to J.B.S.Haldane" Plenum Press., 49-65 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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