H2A.Z nucleosome positioning has no impact on genetic variation in Drosophila genome.

H2A.Z nucleosome positioning has no impact on genetic variation in Drosophila genome.
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H2A.Z 核小体定位对果蝇基因组的遗传变异没有影响

DOI:
10.1371/journal.pone.0058295
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Jiang C
Jiang C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tang Y;Dong S;Cao X;Zhou Q;Ding G;Jiang C

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核小体占据通过增加酵母、鱼类和人类的突变率或抑制 DNA 修复而导致复杂的序列变异率异质性。 H2A.Z核小体广泛参与基因转录激活和调控。为了测试 H2A.Z 核小体是否对果蝇基因组中的序列变异具有类似的影响,我们分析了基因末端和剪接位点的 H2A.Z 核小体占有率和序列变异率。与之前的研究一致,H2A.Z 核小体定位有助于划分外显子的边界。核小体占据与转录起始位点和剪接位点侧翼区域的序列分歧率呈反相关。然而,无论核小体占据、模糊性、启动子中的定位、编码和基因间区域、年轻基因还是老基因,接头 DNA 和 H2A.Z 核小体 DNA 之间不存在速率异质性。但基因间核小体和侧翼连接区的比率高于基因对应物的比率。进一步分析发现,启动子区域(通常是核小体缺失区域)的高序列分歧率可能是由于富集的串联重复序列中的高突变率造成的。有趣的是,在跨越剪接位点的核小体中,核小体 DNA 的序列变异性从外显子内的一端到突出到内含子的另一端显着增加。内含子中宽松的功能限制有助于核小体DNA在内含子中的高驻留率,而外显子中严格的功能限制维持外显子中核小体DNA的低驻留率。总的来说,H2A.Z 核小体占据对果蝇基因组的序列变异性没有影响,这可能是由局部序列组成和伴随的选择压力决定的。
Nucleosome occupancy results in complex sequence variation rate heterogeneity by either increasing mutation rate or inhibiting DNA repair in yeast, fish, and human. H2A.Z nucleosome is extensively involved in gene transcription activation and regulation. To test whether H2A.Z nucleosome has the similar impact on sequence variability in the Drosophila genome, we profiled the H2A.Z nucleosome occupancy and sequence variation rate at gene ends and splicing sites. Consistent with previous studies, H2A.Z nucleosome positioning helps to demarcate the borders of exons. Nucleosome occupancy is anticorrelated with sequence divergence rate in the regions flanking transcription start sites and splicing sites. However, there is no rate heterogeneity between the linker DNA and H2A.Z nucleosomal DNA regardless of nucleosome occupancy, fuzziness, positioning in promoter, coding, and intergenic regions, young or old genes. But the rate at intergenic nucleosomes and the flanking linker regions is higher than that at the genic counterparts. Further analyses found that the high sequence divergence rate in the promoter regions that are usually nucleosome depleted regions may be likely resulted from the high mutation rate in the enriched tandem repeats. Interestingly, within nucleosomes spanning splicing sites, sequence variability of nucleosomal DNA significantly increases from the end within exons to the other end protruding into introns. The relaxed functional constraint in introns contributes to the high rate of nucleosomal DNA residing in introns while the strict functional constraint in exons maintains the low rate of nucleosomal DNA residing in exons. Taken together, H2A.Z nucleosome occupancy has no effect on sequence variability of Drosophila genome, which is likely determined by local sequence composition and the concomitant selection pressure.
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