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addict_cy金虫 (小有名气)
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人特有基因的LncRNA起源新机制
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新paper刚出来，希望感兴趣的朋友讨论 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. 相关新闻 近日，北京大学分子医学研究所李川昀课题组与何爱彬研究员合作，发现43例人特有的蛋白编码基因，并提出了新功能蛋白的长非编码RNA（lncRNA）起源机制。题为“Emergence, Retention and Selection: A Trilogy of Origination forFunctional De Novo Proteins from Ancestral LncRNAs in Primates” 的研究论文在《PLoS Genetics》杂志发表。 认识人之所以为人的分子机制，特别是探究人类特有基因的起源规律，是当代前沿科学问题。李川昀课题组长期运用恒河猴作为人类近缘模式动物的优势，以猴为视角探究人类演化。他们精细解读了猴基因组与转录组，构建了猴基因组学研究平台--RhesusBase，并在国际上首次建立了蛋白与lncRNA的演化关系，形成了一个别具特色的研究方向。 在前期工作积累的基础上，本项研究发现43个人类特有的蛋白编码基因，在猴、黑猩猩等物种中的对应区域并不编码蛋白质，其转录产物是以lncRNA的形式存在。这些区域在序列上具有GC富集的特征，可能为新基因形成并维持稳定的开放读码框（Open Reading Frame）提供了基础。 这些新基因产生的新蛋白究竟是否已获得生物学功能，或仅代表翻译过程中无意义的随机产物？为了阐明这个问题，作者借助群体遗传学分析发现，这些新基因正经历着显著的负向自然选择作用（Purifying Selection），提示它们正在发挥重要的生物学功能。进一步，这些新基因是如何与其它基因相互作用，产生人类特有性状的呢？这个问题的答案目前还不得而知，有待于今后深入系统的研究。 本研究的意义在于一窥人类基因起源与进化的奥秘，同时为揭示大量存在的lncRNA的生物学意义提供了新视角。北京大学分子医学研究所陈加余、申晴同学为本文共同第一作者。本研究受到国家自然科学基金、国家973项目等支持。 |
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