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Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells

机译:斑马鱼生殖细胞和非生殖细胞之间的mtDNA瓶颈强度和时间差异

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We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 x 10^6 mtDNA molecules with high variation between oocytes. During embryogenesis, the mtDNA copy number decreases to ~170 mtDNA molecules per primordial germ cell (PGC), a number similar to that in mammals, and to ~50 per non-PGC. These occur at the same developmental stage, implying considerable variation in mtDNA copy number in (non-)PGCs of the same female, dictated by variation in the mature oocyte. The presence of oocytes with low mtDNA numbers, if similar in humans, could explain how (de novo) mutations can reach high mutation loads within a single generation. High mtDNA copy numbers in mature oocytes are established by mtDNA replication during oocyte development. Bottleneck differences between germline and non-germline cells, due to early differentiation of PGCs, may account for different distribution patterns of familial mutations.
机译:我们研究了斑马鱼的mtDNA瓶颈,以阐明种系和非种系细胞的大小,时间和变异。成熟的斑马鱼卵母细胞平均含有19.0 x 10 ^ 6 mtDNA分子,卵母细胞之间的变异很大。在胚胎发生过程中,每个原始生殖细胞(PGC)的mtDNA拷贝数减少至〜170 mtDNA分子,与哺乳动物的数量相似,而每个非PGC的mtDNA拷贝数减少至〜50。这些发生在相同的发育阶段,这意味着由成熟卵母细胞的变异决定,同一雌性(非)PGCs的mtDNA拷贝数存在显着差异。 mtDNA数量少的卵母细胞的存在,如果在人类中相似的话,可以解释(从头)突变如何在一代人的时间内达到高的突变负荷。成熟卵母细胞中较高的mtDNA拷贝数是通过卵母细胞发育过程中的mtDNA复制建立的。由于PGC的早期分化,种系细胞和非种系细胞之间的瓶颈差异可能解释了家族性突变的不同分布方式。

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