The transcript-centric mutations in human genomes.
The transcript-centric mutations in human genomes.
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DOI：
10.1016/s1672-0229(11)60029-6
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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：
--
作者：
Cui P;Lin Q;Ding F;Hu S;Yu J
由于人类基因组大部分是转录的，因此遗传变异必须表现出反映转录过程和染色体结构之间关系的序列特征，正如我们在单细胞生物中观察到的那样。在这项研究中，一组存在于生殖细胞中的646个普遍存在的表达不变基因（EIGs）被定义并基于来自多个高通量转录组数据的RNA测序数据进行检查。我们基于单核苷酸多态性（SNP）数据证明了人类基因组中基因表达水平与转录本中心突变之间的关系。基因表达与突变之间存在显著的正相关，其中高表达基因比低表达基因积累更多的突变。此外，我们发现了人类基因组中四种主要的转录中心突变类型：C→T，A→G，C→G和G→T，并确定了从转录单位（TU）的5′端到3′端的序列变异的负梯度。跨TU的这些遗传变异的周期性发生与核小体定相相关。我们认为转录中心突变是基因和基因组进化的主要驱动力之一，沿着新基因的产生、基因/基因组复制和水平基因转移。
Since the human genome is mostly transcribed, genetic variations must exhibit sequence signatures reflecting the relationship between transcription processes and chromosomal structures as we have observed in unicellular organisms. In this study, a set of 646 ubiquitous expression-invariable genes (EIGs) which are present in germline cells were defined and examined based on RNA-sequencing data from multiple high-throughput transcriptomic data. We demonstrated a relationship between gene expression level and transcript-centric mutations in the human genome based on single nucleotide polymorphism (SNP) data. A significant positive correlation was shown between gene expression and mutation, where highly-expressed genes accumulate more mutations than lowly-expressed genes. Furthermore, we found four major types of transcript-centric mutations: C→T, A→G, C→G, and G→T in human genomes and identified a negative gradient of the sequence variations aligning from the 5′ end to the 3′ end of the transcription units (TUs). The periodical occurrence of these genetic variations across TUs is associated with nucleosome phasing. We propose that transcript-centric mutations are one of the major driving forces for gene and genome evolution along with creation of new genes, gene/genome duplication, and horizontal gene transfer.