Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, 01854.
Comparative Media Studies/Writing, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
Evolution. 2021 Mar;75(3):706-718. doi: 10.1111/evo.14184. Epub 2021 Feb 6.
Gene duplication is an important driver of genomic diversity that can promote adaptive evolution. However, like most mutations, a newly duplicated gene is often deleterious and removed from the genome by drift or natural selection. The early molecular changes that occur soon after duplication therefore may influence the long-term survival of gene duplicates, but relatively little empirical data exist on the events near the onset of duplication before mutations have time to accumulate. In this study, we contrast gene expression and DNA methylation levels of duplicate genes in the threespine stickleback, Gasterosteus aculeatus, including recently emerged duplications that segregate as copy number variations (CNVs). We find that younger duplicate genes have higher levels of promoter methylation than older genes, and that gene CNVs have higher promoter methylation than non-CNVs. These results suggest preferential duplication of highly methylated genes or rapid methylation changes soon after duplication. We also find a negative association between methylation and expression, providing a putative role for methylation in suppressing transcription that compensates for increases in gene copy numbers and promoting paralog retention. We propose that methylation contributes to the longevity of young duplicate genes, extending the window of opportunity for functional divergence via mutation.
基因复制是基因组多样性的重要驱动因素，可促进适应性进化。然而，与大多数突变一样，新复制的基因通常是有害的，并通过漂变或自然选择从基因组中消除。因此，在突变有时间积累之前，复制后很快发生的早期分子变化可能会影响基因复制的长期存活，但关于复制起始附近发生的事件的经验数据相对较少。在这项研究中，我们对比了三刺鱼（Gasterosteus aculeatus）中重复基因的表达和 DNA 甲基化水平，包括作为拷贝数变异（CNV）分离的新出现的重复基因。我们发现，年轻的重复基因的启动子甲基化水平高于年老的基因，而基因 CNV 的启动子甲基化水平高于非 CNV。这些结果表明，高度甲基化的基因优先复制，或者在复制后很快发生快速的甲基化变化。我们还发现了甲基化与表达之间的负相关，这表明甲基化在抑制转录方面发挥了作用，补偿了基因拷贝数的增加，并促进了同源基因的保留。我们提出，甲基化有助于年轻重复基因的长寿，通过突变延长了功能分化的机会之窗。
