マウスにおけるmtDNA遺伝様式:母性遺伝と急調分離  [in Japanese] Two modes of mitochondrial DNA transmission in mice: Maternal inheritance and rapid segregation  [in Japanese]

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Abstract

哺乳動物には,2種類のゲノム,核DNAとミトコンドリアDNA(mtDNA)が存在している.mtDNAの遺伝様式は,母性遺伝と急調分離に代表されるように,核DNAとは大きく異なる.<BR> mtDNAは古くから母性遺伝をすることが信じられてきた.なぜなら,哺乳動物では卵に存在するmtDNAコピー数が精子よりも10<SUP>3-4</SUP>倍多く,極微量の精子由来mtDNAが次世代へと伝達されることが考えにくかったためである.しかし,当時の技術ではこの極微量の"精子由来のmtDNA"が検出されず,父親由来のmtDNAが子孫へ伝達している可能性が残されていた.その後,高感度なPCR法を用いることで,マウス精子のmtDNAが前核期後期までに消失することが示され,幾つかの特殊な事例を除き,mtDNAは完全に母性遺伝することが,実験的に証明された.形態学的解析からもマウスでは受精時に卵細胞質内に侵入した精子由来ミトコンドリアが2細胞期までにほぼ消失する様子が観察されており,ユビキチン‐プロテアソーム分解系の関与が報告されている.<BR> 一方,急調分離とはmtDNAの状態がヘテロプラズミーからホモプラズミーへ速やかに移行する遺伝現象である.mtDNAは体細胞では10<SUP>3-4</SUP>コピー存在しており,核DNAの約1-10倍も変異を起こしやすい.このことから,ヘテロプラズミーの方がホモプラズミーより起こりやすいことが想定されるが,実際はその逆で一つの細胞に複数のmtDNA分子種が存在することは極めて稀である.このホモプラズミー維持の機構が「ボトルネック効果」であり,これまで「雌性生殖系の細胞中のmtDNA数が極端に減少する」としたモデルが広く受入れられてきた.ところが,実際にmtDNA分子数を我々が測定するとそのコピー数に極端な減少は無く,ホモプラズミーの維持はコピー数減少以外の機構によってmtDNAの分離単位の実効数が小さくなるためと考えられる.

Two modes of mitochondrial (mtDNA) inheritance, i.e., maternal inheritance and rapid segregation between generations, have been proposed as the characteristic modes of mtDNA transmission in most animals. The occurrence of maternal inheritance of mtDNA has been known for a long time, but direct experimental evidence has been lacking. After the development and widespread applications of sensitive detection techniques, such as polymerase chain reaction (PCR), researchers reported paternal (biparental) inheritance of mtDNA in several species. In the case of intraspecific hybrid mice, sperm mtDNA was detected until the early pronuclear stage, but was not detected after 2-cell stage. By contrast, in the case of interspecific hybrid mice, paternal mtDNA was detected throughout the developmental period, from pronuclear to neonatal stages. However, the leakage of paternal mtDNA was limited to the progeny of the first generation of an interspecific cross and did not occur in the progeny of any other generation from subsequent backcrosses. These observations suggest that maternal inheritance of mtDNA is strictly preserved in mice.<BR>   Rapid segregation is the other unique mode of mtDNA transmission. It is unclear why mtDNA sequence variants rapidly segregate through generations, and only 1 variant is fixed in an individual despite the high copy number of mtDNA in somatic cells (10<SUP>3-4</SUP>). To address this question, investigators have proposed the mitochondrial genetic bottleneck that results from the reduction in the number of mtDNA molecules per germ cell. However, in our study, mtDNA copy numbers of female germ cells at several developmental stages was not reduced to the extent that was previously speculated. Therefore, the mitochondrial bottleneck is not generated because of a drastic decline in the mtDNA copy number, but because of a small effective number of segregation units of mtDNA in mouse germ cells.

Journal

  • PLANT MORPHOLOGY

    PLANT MORPHOLOGY 23(1), 35-40, 2011

    The Japanese Society of Plant Morphology

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