Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||The Graduate University for Advanced Studies|
TAKAHATA Naoyuki Coordination Center for Research and Education, 教育研究交流センター, 教授 (30124217)
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
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)
|Keywords||Mhc / T-cell repertoire / Self-nonself discrimination / Mhc restriction / Diversity / Adaptive evolution / DNA sequences / Natural selection / データ解析|
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
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