Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion.
Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion.
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DOI：
10.3390/genes2010169
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发表时间：
2011-02-14
期刊：
影响因子：
3.5
通讯作者：
Shibata T
中科院分区：
文献类型：
--
作者：
Ling F;Mikawa T;Shibata T
线粒体有自己的基因组DNA。与核基因组不同，每个细胞含有数百至数千份线粒体DNA（mtDNA）。由于高频率的诱变，mtDNA的拷贝往往具有异质性序列，但在营养细胞生长期间或通过几个有性世代在细胞内迅速同质化（“同质性”）。异质性与线粒体疾病、糖尿病和衰老密切相关。最近的研究表明，酵母细胞具有使mtDNA均质化的机制，使用具有基因转换的常见DNA加工途径;即，这两个遗传事件都是由双链断裂引发的，双链断裂被加工成3′单链尾。其中一个尾部与受体双链DNA的互补序列碱基配对以形成D环（同源配对），其中启动修复DNA合成以恢复因断裂而丢失的序列。基因转换产生序列多样性，这取决于供体和受体序列之间的差异，特别是当它发生在具有一些序列变异的DNA序列家族的许多拷贝之间时，例如在鸡的免疫球蛋白多样化中。线粒体DNA可以看作是一个序列家族，其中的成员往往是多样化的自发突变的频率高。因此，这将是有趣的，以确定为什么和如何双链断裂和D-环的形成诱导序列同质化的线粒体和序列多样化的核DNA。我们将回顾线粒体DNA同质性的机制和作用，与核基因转换，多样化的基因和基因组序列，提供线索，了解如何共同的DNA加工途径导致这种不同的结果。
Mitochondria have their own genomic DNA. Unlike the nuclear genome, each cell contains hundreds to thousands of copies of mitochondrial DNA (mtDNA). The copies of mtDNA tend to have heterogeneous sequences, due to the high frequency of mutagenesis, but are quickly homogenized within a cell (“homoplasmy”) during vegetative cell growth or through a few sexual generations. Heteroplasmy is strongly associated with mitochondrial diseases, diabetes and aging. Recent studies revealed that the yeast cell has the machinery to homogenize mtDNA, using a common DNA processing pathway with gene conversion; i.e., both genetic events are initiated by a double-stranded break, which is processed into 3′ single-stranded tails. One of the tails is base-paired with the complementary sequence of the recipient double-stranded DNA to form a D-loop (homologous pairing), in which repair DNA synthesis is initiated to restore the sequence lost by the breakage. Gene conversion generates sequence diversity, depending on the divergence between the donor and recipient sequences, especially when it occurs among a number of copies of a DNA sequence family with some sequence variations, such as in immunoglobulin diversification in chicken. MtDNA can be regarded as a sequence family, in which the members tend to be diversified by a high frequency of spontaneous mutagenesis. Thus, it would be interesting to determine why and how double-stranded breakage and D-loop formation induce sequence homogenization in mitochondria and sequence diversification in nuclear DNA. We will review the mechanisms and roles of mtDNA homoplasmy, in contrast to nuclear gene conversion, which diversifies gene and genome sequences, to provide clues toward understanding how the common DNA processing pathway results in such divergent outcomes.
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影响因子：
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64.5
作者：
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Chinnery, Patrick F.
DOI：
10.1073/pnas.93.20.10735
发表时间：
1996-10-01
影响因子：
11.1
作者：
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通讯作者：
Seeberg, E