Distinct contributions of replication and transcription to mutation rate variation of human genomes.
Distinct contributions of replication and transcription to mutation rate variation of human genomes.
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DOI：
10.1016/s1672-0229(11)60028-4
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Yu J
中科院分区：
文献类型：
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作者：
Cui P;Ding F;Lin Q;Zhang L;Li A;Zhang Z;Hu S;Yu J
在这里，我们评估了两个主要的生物过程-DNA复制和转录-在人类基因组中的突变率变化的贡献。基于对公开的人类组织转录组学数据、Hela细胞高分辨率复制图谱和dbSNP数据的分析，我们提出了表达宽度、局部区域复制时间和SNP密度之间的显著相关性。组织特异性（TS）基因的SNP密度显著高于管家基因（HK）。TS基因倾向于位于复制后期的基因组区域，并且与复制早期区域相比，这些区域中的基因具有更高的SNP密度。此外，SNP密度与HK基因的表达水平呈正相关。我们的结论是，DNA复制过程产生更强的突变压力比转录相关的生物过程做，导致TS基因的突变率增加，而对HK基因的影响较弱。相反，转录相关过程主要负责高表达HK基因突变的积累。
Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.