PNAS;浙江大学杜继曾和陈学群教授解析甲基化与物种形成
2月18日，国际著名学术期刊《美国国家科学院院刊》在线发表浙江大学医学院的杜继曾教授、陈学群教授和Haifa大学Eviatar Nevo研究团队联合揭示了同域物种形成中的p53适应性甲基化调控。同域物种形成理论认为，同一区域的种群可以进化出生殖隔离的新物种。文章通讯作者是浙江大学医学院的杜继曾教授、陈学群教授和Haifa大学的Eviatar Nevo。
研究显示，这两种盲鼹形鼠之间存在p53及其靶基因的差异性表达。而p53的差异性表达是其启动子甲基化造成的，启动子的甲基化差异影响了一些转录因子的结合。进一步研究表明，S. galili的这种p53差异性表达，有选择地改变了适应性的细胞周期阻滞。这项研究为S. galili的同域物种形成提供了支持，展示了表观遗传学修饰在适应性进化中的重要性。
原文链接：
Adaptive methylation regulation of p53 pathway in sympatric speciation of blind mole rats, Spalax
原文摘要：
Epigenetic modifications play significant roles in adaptive evolution. The tumor suppressor p53, well known for controlling cell fate and maintaining genomic stability, is much less known as a master gene in environmental adaptation involving methylation modifications. The blind subterranean mole rat Spalax eherenbergi superspecies in Israel consists of four species that speciated peripatrically. Remarkably, the northern Galilee species Spalax galili (2n = 52) underwent adaptive ecological sympatric speciation, caused by the sharply divergent chalk and basalt ecologies. This was demonstrated by mitochondrial and nuclear genomic evidence. Here we show that the expression patterns of the p53 regulatory pathway diversified between the abutting sympatric populations of S. galili in sharply divergent chalk–basalt ecologies. We identified higher methylation on several sites of the p53 promoter in the population living in chalk soil (chalk population). Site mutagenesis showed that methylation on these sites linked to the transcriptional repression of p53 involving Cut-Like Homeobox 1 (Cux1), paired box 4 (Pax 4), Pax 6, and activator protein 1 (AP-1). Diverse expression levels of p53 between the incipiently sympatrically speciating chalk–basalt abutting populations of S. galili selectively affected cell-cycle arrest but not apoptosis. We hypothesize that methylation modification of p53 has adaptively shifted in supervising its target genes during sympatric speciation of S. galili to cope with the contrasting environmental stresses of the abutting divergent chalk–basalt ecologies.
作者：杜继曾和陈学群
