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(guó)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)人類基因組中以轉(zhuǎn)錄為中心的突變研究方面取得新進(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（Transcription-coupled DNA Repair，TCR）有關(guān),。最后,，研究還提出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)60029-6
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The Transcript-centric Mutations in Human Genomes
Peng Cui, Qiang Lin, Feng Ding, Songnian Hu, Jun Yu
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.
