Babak Tomas, DeVeale Brian, Tsang Emily K, Zhou Yiqi, Li Xin, Smith Kevin S, Kukurba Kim R, Zhang Rui, Li Jin Billy, van der Kooy Derek, Montgomery Stephen B, Fraser Hunter B
Department of Biology, Stanford University, Stanford, California, USA.
University of California San Francisco School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Nat Genet. 2015 May;47(5):544-9. doi: 10.1038/ng.3274. Epub 2015 Apr 13.
Genomic imprinting is an epigenetic process that restricts gene expression to either the maternally or paternally inherited allele. Many theories have been proposed to explain its evolutionary origin, but understanding has been limited by a paucity of data mapping the breadth and dynamics of imprinting within any organism. We generated an atlas of imprinting spanning 33 mouse and 45 human developmental stages and tissues. Nearly all imprinted genes were imprinted in early development and either retained their parent-of-origin expression in adults or lost it completely. Consistent with an evolutionary signature of parental conflict, imprinted genes were enriched for coexpressed pairs of maternally and paternally expressed genes, showed accelerated expression divergence between human and mouse, and were more highly expressed than their non-imprinted orthologs in other species. Our approach demonstrates a general framework for the discovery of imprinting in any species and sheds light on the causes and consequences of genomic imprinting in mammals.
基因组印记是一种表观遗传过程,它将基因表达限制在母本或父本遗传的等位基因上。人们提出了许多理论来解释其进化起源,但由于缺乏描绘任何生物体中印迹的广度和动态的数据,相关理解一直受到限制。我们生成了一个涵盖33个小鼠和45个人类发育阶段及组织的印记图谱。几乎所有印记基因在早期发育中就被印记,并且在成年期要么保留其亲本来源的表达,要么完全丧失。与亲本冲突的进化特征一致,印记基因富含母本和父本表达基因的共表达对,在人和小鼠之间表现出加速的表达差异,并且比其他物种中的非印记直系同源基因表达更高。我们的方法展示了在任何物种中发现印记的通用框架,并揭示了哺乳动物基因组印记的原因和后果。