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addict_cy金蟲 (小有名氣)
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[交流]
人特有基因的LncRNA起源新機制
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新paper剛出來，希望感興趣的朋友討論 Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates Abstract While some human-specific protein-coding genes have been proposed to originate from ancestral lncRNAs, the transition process remains poorly understood. Here we identified 64 hominoid-specific de novo genes and report a mechanism for the origination of functional de novo proteins from ancestral lncRNAs with precise splicing structures and specific tissue expression profiles. Whole-genome sequencing of dozens of rhesus macaque animals revealed that these lncRNAs are generally not more selectively constrained than other lncRNA loci. The existence of these newly-originated de novo proteins is also not beyond anticipation under neutral expectation, as they generally have longer theoretical lifespan than their current age, due to their GC-rich sequence property enabling stable ORFs with lower chance of non-sense mutations. Interestingly, although the emergence and retention of these de novo genes are likely driven by neutral forces, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution, which may contribute to human-specific genetic novelties by taking advantage of existed genomic contexts. Author Summary Although gene duplication has been believed as a predominant mechanism for creating new genes, recent reports suggested that new proteins could evolve “de novo” from non-coding DNA regions. These de novo genes are also named as “motherless” genes due to their lack of ancestral proteins as precursors, while recently we and others found that lncRNAs may represent an intermediate stage of their origination. To further elucidate this lncRNA-protein transition process, here we identified 64 hominoid-specific de novo genes and report a new mechanism for the origination of functional de novo proteins from ancestral non-coding transcripts: These non-coding “precursors” are generally not more selectively constrained than other lncRNA loci; and the existence of these de novo proteins is not beyond anticipation under neutral expectation; however, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution. 相關(guān)新聞 近日，北京大學(xué)分子醫(yī)學(xué)研究所李川昀課題組與何愛彬研究員合作，發(fā)現(xiàn)43例人特有的蛋白編碼基因，并提出了新功能蛋白的長非編碼RNA（lncRNA）起源機制。題為“Emergence, Retention and Selection: A Trilogy of Origination forFunctional De Novo Proteins from Ancestral LncRNAs in Primates” 的研究論文在《PLoS Genetics》雜志發(fā)表。 認(rèn)識人之所以為人的分子機制，特別是探究人類特有基因的起源規(guī)律，是當(dāng)代前沿科學(xué)問題。李川昀課題組長期運用恒河猴作為人類近緣模式動物的優(yōu)勢，以猴為視角探究人類演化。他們精細(xì)解讀了猴基因組與轉(zhuǎn)錄組，構(gòu)建了猴基因組學(xué)研究平臺--RhesusBase，并在國際上首次建立了蛋白與lncRNA的演化關(guān)系，形成了一個別具特色的研究方向�！� 在前期工作積累的基礎(chǔ)上，本項研究發(fā)現(xiàn)43個人類特有的蛋白編碼基因，在猴、黑猩猩等物種中的對應(yīng)區(qū)域并不編碼蛋白質(zhì)，其轉(zhuǎn)錄產(chǎn)物是以lncRNA的形式存在。這些區(qū)域在序列上具有GC富集的特征，可能為新基因形成并維持穩(wěn)定的開放讀碼框（Open Reading Frame）提供了基礎(chǔ)。 這些新基因產(chǎn)生的新蛋白究竟是否已獲得生物學(xué)功能，或僅代表翻譯過程中無意義的隨機產(chǎn)物？為了闡明這個問題，作者借助群體遺傳學(xué)分析發(fā)現(xiàn)，這些新基因正經(jīng)歷著顯著的負(fù)向自然選擇作用（Purifying Selection），提示它們正在發(fā)揮重要的生物學(xué)功能。進(jìn)一步，這些新基因是如何與其它基因相互作用，產(chǎn)生人類特有性狀的呢？這個問題的答案目前還不得而知，有待于今后深入系統(tǒng)的研究。 本研究的意義在于一窺人類基因起源與進(jìn)化的奧秘，同時為揭示大量存在的lncRNA的生物學(xué)意義提供了新視角。北京大學(xué)分子醫(yī)學(xué)研究所陳加余、申晴同學(xué)為本文共同第一作者。本研究受到國家自然科學(xué)基金、國家973項目等支持。 |
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