基因突變會(huì)導(dǎo)致人類疾病的產(chǎn)生,，因此研究遺傳變異的產(chǎn)生過程和那些能夠引起疾病的突變對(duì)生命科學(xué)基礎(chǔ)研究以及人類健康是十分關(guān)鍵和重要的。近日,，中國科學(xué)院北京基因組研究所于軍研究員帶領(lǐng)其研究團(tuán)隊(duì),，在有關(guān)人類基因組中中以轉(zhuǎn)錄為中心的突變研究取得新進(jìn)展，相關(guān)研究成果在Genomics, Proteomics & Bioinformatics雜志上發(fā)表,。
該研究組崔鵬博士等人,，通過對(duì)人類10種不同組織的高通量RNA測(cè)序數(shù)據(jù)和SNP（單核苷酸多態(tài)性）數(shù)據(jù)進(jìn)行分析，研究了人類基因組的轉(zhuǎn)錄突變過程,，對(duì)人類基因突變的基本法則提出了新的見解,。研究結(jié)果顯示，人類基因組中基因突變率與它們的表達(dá)水平成正相關(guān),。這說明突變并不是隨機(jī)產(chǎn)生的,，而更傾向于在那些表達(dá)頻率更高和表達(dá)量更高的基因中產(chǎn)生并累積。此外,，他們通過研究12種類型的核苷酸突變頻率,，發(fā)現(xiàn)C→T，A→G,，C→G,，和G→T是人類基因組的四種主要轉(zhuǎn)錄突變類型。同時(shí),，研究也表明,，突變修復(fù)率從轉(zhuǎn)錄本的5′端到3′端呈下降趨勢(shì)，并且下降幅度與基因表達(dá)水平相關(guān),，這可能與轉(zhuǎn)錄偶聯(lián)的DNA分子修復(fù)過程有關(guān)（Transcription-coupled DNA Repair,，TCR）,。最后，研究還提出了人類基因組遺傳變異的周期性應(yīng)該是核小體定位和TCR作用的共同結(jié)果,。
該研究表明人類基因組以轉(zhuǎn)錄為中心的突變是基因和基因組進(jìn)化的主要驅(qū)動(dòng)力之一,，為人類基因突變研究提供了新的思路。（生物谷Bioon.com）
doi:10.1016/S1672-0229(11)60028-4
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Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes
Peng Cuia, #, Feng Dinga, #, Qiang Lina, #, Lingfang Zhanga, Ang Lib, Zhang Zhanga, Songnian Hua, , , Jun Yua, ,
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.
