Potential non-B DNA regions in the human genome are associated with higher rates of nucleotide mutation and expression variation.
Potential non-B DNA regions in the human genome are associated with higher rates of nucleotide mutation and expression variation.
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DOI：
10.1093/nar/gku921
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发表时间：
2014-11-10
影响因子：
14.9
通讯作者：
Przytycka TM
中科院分区：
文献类型：
--
作者：
Du X;Gertz EM;Wojtowicz D;Zhabinskaya D;Levens D;Benham CJ;Schäffer AA;Przytycka TM
虽然个别非B DNA结构已被证明会影响基因表达，但其广泛的调控作用仍然难以捉摸。我们利用基因组变异和表达数量性状基因座（eQTL）数据来分析潜在的非B DNA区域的全基因组变异倾向及其与基因表达的关系。独立于基因组位置，这些区域富含核苷酸变体。我们的研究结果与以前观察到的这些区域的致突变性是一致的，并反驳了以前的研究结论，即G-四链体区域的变异频率降低。虽然这种致突变性可能会破坏这些元素的功能，我们确定在潜在的非B DNA区域的负选择的签名。然而，我们发现在潜在的非B DNA区域的eQTL相关的变体的耗尽，相反，可能是从他们提出的监管作用的预期。然而，我们也观察到潜在的非B DNA区域的下游基因在个体之间表现出更高的表达变异。这种致突变性和下游基因表达变异性的耐受性之间的耦合可能是进化适应的结果，这使得非B DNA结构的致突变性与其在功能重要区域的位置及其潜在的调节作用相一致。
While individual non-B DNA structures have been shown to impact gene expression, their broad regulatory role remains elusive. We utilized genomic variants and expression quantitative trait loci (eQTL) data to analyze genome-wide variation propensities of potential non-B DNA regions and their relation to gene expression. Independent of genomic location, these regions were enriched in nucleotide variants. Our results are consistent with previously observed mutagenic properties of these regions and counter a previous study concluding that G-quadruplex regions have a reduced frequency of variants. While such mutagenicity might undermine functionality of these elements, we identified in potential non-B DNA regions a signature of negative selection. Yet, we found a depletion of eQTL-associated variants in potential non-B DNA regions, opposite to what might be expected from their proposed regulatory role. However, we also observed that genes downstream of potential non-B DNA regions showed higher expression variation between individuals. This coupling between mutagenicity and tolerance for expression variability of downstream genes may be a result of evolutionary adaptation, which allows reconciling mutagenicity of non-B DNA structures with their location in functionally important regions and their potential regulatory role.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.9
作者：
Cooper, David N.;Bacolla, Albino;Ferec, Claude;Vasquez, Karen M.;Kehrer-Sawatzki, Hildegard;Chen, Jian-Min
通讯作者：
Chen, Jian-Min
影响因子：
14.9
作者：
Baral A;Kumar P;Halder R;Mani P;Yadav VK;Singh A;Das SK;Chowdhury S
通讯作者：
Chowdhury S
影响因子：
14.9
作者：
Benson DA;Cavanaugh M;Clark K;Karsch-Mizrachi I;Lipman DJ;Ostell J;Sayers EW
通讯作者：
Sayers EW
DOI：
10.1073/pnas.79.21.6465
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HAMADA, H;PETRINO, MG;KAKUNAGA, T
通讯作者：
KAKUNAGA, T