Szedlak Anthony, Smith Nicholas, Liu Li, Paternostro Giovanni, Piermarocchi Carlo
Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan, United States of America.
Salgomed Inc., Del Mar, California, United States of America.
PLoS Comput Biol. 2016 Jun 30;12(6):e1005009. doi: 10.1371/journal.pcbi.1005009. eCollection 2016 Jun.
The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics.
当今生命形式中存在的多样、专门化的基因是从古老的基本基因的共同核心进化而来的。然而，这些基因并非单独进化：基因表达由一个复杂的相互作用网络控制，一个基因的改变可能会驱动其蛋白质结合伙伴的相互变化。与许多复杂网络一样，这些基因调控网络（GRN）由群落或具有相对高连通性的基因簇组成。深入了解单个基因的进化历史与基础GRN的拓扑特性之间的关系对于进化遗传学至关重要。在这里，我们表明急性髓系白血病GRN和一般人类GRN的拓扑特性与其基因的进化特性紧密相关。进化缓慢（“冷”）的古老基因倾向于相互作用，进化迅速（“热”）的年轻基因也是如此。这自然导致基因分离成具有相对同质进化历史的群落结构。我们认为基因复制将古老、“冷”的基因和群落置于网络中心，而年轻、“热”的基因和群落置于外围。我们用单节点中心性度量以及两种新的效率度量——集效率和集间效率来证明这一点。我们得出结论，这些研究GRN群落结构与其基因进化特性之间关系的方法为理解进化遗传学提供了新的视角。
