GC-biased gene conversion in yeast is specifically associated with crossovers: molecular mechanisms and evolutionary significance.

GC-biased gene conversion in yeast is specifically associated with crossovers: molecular mechanisms and evolutionary significance.
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DOI:
10.1093/molbev/mst056
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发表时间:
2013-06
影响因子:
10.7
通讯作者:
Duret L
Duret L
中科院分区:
生物学1区
文献类型:
--
作者:
Lesecque Y;Mouchiroud D;Duret L

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GC偏倚基因转化(gBGC)是减数分裂过程中GC等位基因比AT等位基因更容易传递的重组过程。在许多真核生物中,gBGC在基因组进化中起着重要作用。然而,gBGC的分子机制尚不清楚。重组过程的不同步骤可能导致gBGC:双链断裂(DSBs)的形成,同源或姐妹染色单体的入侵,以及异源双链错配的修复。为了研究这些模型,我们分析了酿酒酵母(Saccharomyces cerevisiae)的杂交(COs)和非杂交(NCOs)全基因组数据集。我们证明了GC等位基因的过传递是COs特有的,并且它发生在所有等位基因都来自同一供体单倍型的转化束中。因此,gBGC产生于一个导致长补丁修复的过程。我们发现gBGC与较长的束相关,并且它是由位于束末端的等位基因的性质(GC或AT)驱动的。这些观察结果推翻了gBGC是由于碱基切除修复机制或DSB形成偏差造成的假设,并表明在酿酒葡萄球菌中,gBGC是由错配修复(MMR)系统引起的。我们提出,在CO分解过程中,两条DNA链上的缺口可能是导致MMR活性偏差的原因。我们的观察结果与假设一致,即gBGC是限制有丝分裂细胞突变率的选择压力的非适应性结果。
GC-biased gene conversion (gBGC) is a process associated with recombination that favors the transmission of GC alleles over AT alleles during meiosis. gBGC plays a major role in genome evolution in many eukaryotes. However, the molecular mechanisms of gBGC are still unknown. Different steps of the recombination process could potentially cause gBGC: the formation of double-strand breaks (DSBs), the invasion of the homologous or sister chromatid, and the repair of mismatches in heteroduplexes. To investigate these models, we analyzed a genome-wide data set of crossovers (COs) and noncrossovers (NCOs) in Saccharomyces cerevisiae. We demonstrate that the overtransmission of GC alleles is specific to COs and that it occurs among conversion tracts in which all alleles are converted from the same donor haplotype. Thus, gBGC results from a process that leads to long-patch repair. We show that gBGC is associated with longer tracts and that it is driven by the nature (GC or AT) of the alleles located at the extremities of the tract. These observations invalidate the hypotheses that gBGC is due to the base excision repair machinery or to a bias in DSB formation and suggest that in S. cerevisiae, gBGC is caused by the mismatch repair (MMR) system. We propose that the presence of nicks on both DNA strands during CO resolution could be the cause of the bias in MMR activity. Our observations are consistent with the hypothesis that gBGC is a nonadaptive consequence of a selective pressure to limit the mutation rate in mitotic cells.
DOI: 10.1093/emboj/19.13.3408
发表时间: 2000-07-03
期刊: EMBO JOURNAL
影响因子: 11.4
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