2016年6月13日，国际分子生物学和进化领域的权威期刊《molecular Biology and evolution》杂志上在线发表了华中农业大学信息学院张红雨教授生物信息团队题为“Spatial colocalization of human ohnologpairs acts to maintain dosage-balance”的研究论文。研究论文报导了人类基因中全基因组倍增事件后保留下来的重复基因(ohnolog)在三维空间上彼此靠近，并提出这种空间邻近有利于维持重复基因的剂量平衡。信息学院博士生谢婷和青年教师杨庆勇副教授是该论文的并列**作者，都柏林大学三一学院Aoife McLysaght教授及我校张红雨教授为该论文的通讯作者，信息学院为**完成单位。
在人类基因漫长的进化历程中，基因组被完整地复制过两次。理论上，复制带来了基因的大量冗余，大部分复制基因会很快丢失。但实际上，人类基因组中大概1/3的复制基因一直保留至今。“为什么这么多的重复基因被保留下来?”这个疑问，一直是人类基因组进化研究的重点。该论文利用高质量的人类基因组三维结构数据，结合基因拷贝数变异、基因共表达及功能注释信息，发现人类基因组中复制基因及其搭档虽然位于不同染色体上，但两者在空间上相互靠近。这些具有空间邻近特征的“重复基因对”具有更高的共表达趋势、基因功能相似性及更低的拷贝数变异，并且这些基因上的突变更容易导致遗传病。据此，该研究认为重复基因的空间邻近有利于维持其剂量平衡，这为进一步研究重复基因的保留机制提供了新的思路。在应用方面，该研究有助于筛选**易感基因和**靶标。
原文链接：
Spatial Colocalization of human Ohnolog Pairs Acts to Maintain Dosage-Balance
原文摘要：
Ohnologs – paralogous gene pairs generated by whole genome duplication (WGD) – are enriched for dosage sensitive genes, i.e., genes that have a phenotype due to copy number changes. Dosage sensitive genes frequently occur in the same metabolic pathway and in physically interacting proteins. Accumulating evidence reveals that functionally related genes tend to co-localize in the three dimensional (3D) arrangement of chromosomes. We query whether the spatial distribution of ohnologs has implications for their dosage balance. We analyzed the colocalization frequency of ohnologs based on chromatin interaction datasets of seven human cell lines and found that ohnolog pairs exhibit higher spatial proximity in 3D nuclear organization than other paralog pairs and than randomly chosen ohnologs in the genome. We also found that colocalized ohnologs are more resistant to copy number variations and more likely to be disease-associated genes, which indicates a stronger dosage balance in ohnologs with high spatial proximity. This phenomenon is further supported by the stronger similarity of gene co-expression and of gene ontology (GO) terms of colocalized ohnologs. Additionally, for a large fraction of ohnologs, the spatial colocalization is conserved in mouse cells, suggestive of functional constraint on their 3D positioning in the nucleus.