New genes drive the evolution of gene interaction networks in the human and mouse genomes.
New genes drive the evolution of gene interaction networks in the human and mouse genomes.
复制标题
新基因驱动人类和小鼠基因组中基因相互作用网络的进化
DOI：
10.1186/s13059-015-0772-4
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发表时间：
2015-10-01
期刊：
影响因子：
12.3
通讯作者：
Long M
中科院分区：
文献类型：
--
作者：
Zhang W;Landback P;Gschwend AR;Shen B;Long M
具有新功能的新基因的起源创造了生物体的遗传和表型多样性。为了获得功能角色，新基因必须整合到祖先基因-基因相互作用（GGI）网络中。新基因整合到祖先网络中的机制及其进化意义尚待确定。在此，我们提出了一项研究，调查人类和小鼠基因组中GGI网络的新基因驱动进化的速率和模式。我们通过构建和分析三个不同的GGI数据集来研究起源于人类和小鼠谱系不同阶段的新基因的网络拓扑和功能进化。我们发现，在整个脊椎动物进化过程中，大量新基因整合到GGI网络中。这些基因经历了一个逐渐整合到GGI网络中的过程，从网络外围开始，逐渐成为高度连接的枢纽，并获得多效性和必要功能。我们确定了一些人类谱系特异性的枢纽基因，这些基因进化出了与大脑发育相关的功能。最后，我们探讨了可能的潜在机制，推动GGI网络的演变和观察到的新基因整合过程的模式。我们的研究结果揭示了一个新基因的网络拓扑整合过程：超过5000个新基因整合到人类和小鼠的祖先GGI网络中;新基因逐渐获得越来越多的基因伴侣;一些人类特异性基因进化成具有关键表型效应的枢纽结构。我们的数据为遗传网络的进化提供了新的概念性见解。本文的在线版本（doi：10.1186/s13059-015-0772-4）包含补充材料，可供授权用户使用。
The origin of new genes with novel functions creates genetic and phenotypic diversity in organisms. To acquire functional roles, new genes must integrate into ancestral gene-gene interaction (GGI) networks. The mechanisms by which new genes are integrated into ancestral networks, and their evolutionary significance, are yet to be characterized. Herein, we present a study investigating the rates and patterns of new gene-driven evolution of GGI networks in the human and mouse genomes. We examine the network topological and functional evolution of new genes that originated at various stages in the human and mouse lineages by constructing and analyzing three different GGI datasets. We find a large number of new genes integrated into GGI networks throughout vertebrate evolution. These genes experienced a gradual integration process into GGI networks, starting on the network periphery and gradually becoming highly connected hubs, and acquiring pleiotropic and essential functions. We identify a few human lineage-specific hub genes that have evolved brain development-related functions. Finally, we explore the possible underlying mechanisms driving the GGI network evolution and the observed patterns of new gene integration process. Our results unveil a remarkable network topological integration process of new genes: over 5000 new genes were integrated into the ancestral GGI networks of human and mouse; new genes gradually acquire increasing number of gene partners; some human-specific genes evolved into hub structure with critical phenotypic effects. Our data cast new conceptual insights into the evolution of genetic networks. The online version of this article (doi:10.1186/s13059-015-0772-4) contains supplementary material, which is available to authorized users.