生物
表观遗传学
DNA甲基化
斑马鱼
遗传学
基因
达尼奥
表型
基因沉默
甲基化
进化生物学
基因表达
作者
Aniket V. Gore,Kelly A. Tomins,James R. Iben,Larry Ma,Daniel Castranova,Andrew Davis,Amy Parkhurst,William R. Jeffery,Brant M. Weinstein
标识
DOI:10.1038/s41559-018-0569-4
摘要
Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss-of-eyes phenotype in the Pachón blind cave morph of the Mexican tetra Astyanax mexicanus, no inactivating mutations have been found in any of these genes. Here, we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave A. mexicanus. By performing parallel analyses in A. mexicanus cave and surface morphs, and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and downregulated genes in the cave morph are also linked to human eye disorders, suggesting that the function of these genes is conserved across vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.
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