近日,,中國(guó)科學(xué)院北京基因組研究所于軍研究員和雷紅星研究員合作開展的“人類雙向成對(duì)基因功能網(wǎng)絡(luò)研究”取得階段性進(jìn)展,,其研究論文“Functional Networking of Human Divergently Paired Genes (DPGs)”,于2013年10月在《PLoS ONE》雜志上發(fā)表,。該文對(duì)人類雙向成對(duì)基因(Divergently paired genes, DPGs)的功能網(wǎng)絡(luò)進(jìn)行了全面的分析,。
DPGs又稱雙向表達(dá)基因,,在物種和種系的進(jìn)化過(guò)程中具有較高的保守性,,因而被認(rèn)為在基因組的組織以及功能調(diào)控上具有特殊的地位。盡管先前已有不少學(xué)者對(duì)DPGs的保守性和組織方式做出了研究,,但是DPGs之間的功能關(guān)系一直沒(méi)有很好地被解釋,。
為此,研究人員對(duì)那些可以通過(guò)功能相連的DPGs進(jìn)行了全面的分析,。這些DPGs具有特殊的基因組織結(jié)構(gòu),,同時(shí)包括了核心的細(xì)胞功能以及環(huán)境應(yīng)答相關(guān)的功能(外圍功能),。
研究人員發(fā)現(xiàn)DPGs的基因?qū)A向于參與不同的信號(hào)通路,也就是說(shuō),,通過(guò)一個(gè)啟動(dòng)子序列,,可以實(shí)現(xiàn)同時(shí)調(diào)控兩個(gè)或以上信號(hào)通路的作用。與此同時(shí),,通過(guò)與隨機(jī)的基因?qū)M(jìn)行對(duì)比分析,,研究人員還發(fā)現(xiàn)DPGs的基因?qū)A向于具有相同的細(xì)胞組件和分子功能。由此,,研究人員依據(jù)DPGs基因?qū)Φ倪B接關(guān)系構(gòu)建了功能調(diào)控網(wǎng)絡(luò),。
在這個(gè)調(diào)控網(wǎng)絡(luò)中主要存在3個(gè)功能模塊,其中較大的一個(gè)模塊被認(rèn)為與HKGs相關(guān)并參與了核心的細(xì)胞功能,。同時(shí),,這個(gè)模塊無(wú)論在神經(jīng)組織或是非神經(jīng)組織中,表達(dá)水平均具有較小的差異,?;谵D(zhuǎn)錄組的數(shù)據(jù),研究人員進(jìn)一步指出這個(gè)模塊在HIV以及其他疾?。ㄈ绨┌Y)的致病機(jī)理中,,也起到一定的作用。
基于物種和種系保守性的研究以及在不同組織和疾病中的差異調(diào)控狀況,,研究人員指出DPGs可能包括兩類基因,,一類與管家基因相關(guān),一類與組織特異基因相關(guān),。這一新的發(fā)現(xiàn)對(duì)于DPGs在進(jìn)化上具有較強(qiáng)保守性的原因提供了功能上的解釋,。 (生物谷Bioon.com)
生物谷推薦的英文摘要
PLoS ONE doi:10.1371/journal.pone.0078896
Functional Networking of Human Divergently Paired Genes (DPGs)
Bin Xie,Dapeng Wang,Yong Duan,Jun Yu ,Hongxing Lei
Divergently paired genes (DPGs), also known as bidirectional (head-to-head positioned) genes, are conserved across species and lineages, and thus deemed to be exceptional in genomic organization and functional regulation. Despite previous investigations on the features of their conservation and gene organization, the functional relationship among DPGs in a given species and lineage has not been thoroughly clarified. Here we report a network-based comprehensive analysis on human DPGs and our results indicate that the two members of the DPGs tend to participate in different biological processes while enforcing related functions as modules. Comparing to randomly paired genes as a control, the DPG pairs have a tendency to be clustered in similar “cellular components” and involved in similar “molecular functions”. The functional network bridged by DPGs consists of three major modules. The largest module includes many house-keeping genes involved in core cellular activities. This module also shows low variation in expression in both CNS (central nervous system) and non-CNS tissues. Based on analyses of disease transcriptome data, we further suggest that this particular module may play crucial roles in HIV infection and its disease mechanism.