Dynamics of DNA methylation in recent human and great ape evolution.
Dynamics of DNA methylation in recent human and great ape evolution.
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DOI：
10.1371/journal.pgen.1003763
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Marques-Bonet T
中科院分区：
文献类型：
--
作者：
Hernando-Herraez I;Prado-Martinez J;Garg P;Fernandez-Callejo M;Heyn H;Hvilsom C;Navarro A;Esteller M;Sharp AJ;Marques-Bonet T
DNA甲基化是一种表观遗传修饰，参与调控过程，如发育过程中的细胞分化、X染色体失活、基因组印记和对复杂疾病的易感性。然而，人类及其近亲之间DNA甲基化变化的动态仍然知之甚少。我们使用Illumina Methylation 450微珠阵列对9名人类和23名灵长类动物样本（包括所有种类的类人猿（黑猩猩、倭黑猩猩、大猩猩和猩猩））之间的CpG甲基化模式进行了比较分析。我们的分析在类人猿中发现了10800个甲基化模式发生显著改变的基因，其中包括10170个甲基化模式为人类所独有的基因。其中一些已知与发育和神经学特征有关，这表明表观遗传变化在最近的人类和灵长类动物进化过程中频繁发生。我们确定了一个显着的正相关性之间的编码变异率和甲基化在启动子水平的改变，指示蛋白质序列的进化和基因调控之间的共存。相反，支持人类和类人猿之间的许多表型差异不是由于氨基酸差异的想法，我们的分析还确定了184个基因，这些基因在人类和黑猩猩之间的蛋白质水平上完全保守，但在这两个物种之间显示出显着的表观遗传差异。我们的结论是，表观遗传改变是灵长类动物进化过程中的一个重要力量，并已在进化比较基因组学的探索。人类与其近亲之间的蛋白质编码序列差异太小，无法解释其表型差异。据推测，这些差异可能是由基因调控的改变，而不是主要的基因组序列。DNA甲基化是一种重要的表观遗传修饰，参与许多生物学过程，但从进化的角度来看，这种修饰仍然知之甚少。为此，我们对人类和类人猿之间的CpG甲基化模式进行了比较分析。使用这种方法，我们能够研究最近灵长类动物进化中DNA甲基化的动态，并确定人类和类人猿中显示物种特异性甲基化模式的区域。我们发现，基因的启动子甲基化的改变往往表现出增加的速度，在他们的蛋白质序列的分歧，相反，我们还确定了许多基因的调节变化之间的人类和黑猩猩，具有完全保守的蛋白质序列。我们的研究首次提供了所有类人猿基因组中发生的进化表观遗传变化的全球视角。
DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ∼800 genes with significantly altered methylation patterns among the great apes, including ∼170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics. Differences in protein coding sequences between humans and their closest relatives are too small to account for their phenotypic differences. It has been hypothesized that these differences may be explained by alterations of gene regulation rather than primary genome sequence. DNA methylation is an important epigenetic modification that is involved in many biological processes, but from an evolutionary point of view this modification is still poorly understood. To this end, we performed a comparative analysis of CpG methylation patterns between humans and great apes. Using this approach, we were able to study the dynamics of DNA methylation in recent primate evolution and to identify regions showing species-specific methylation pattern among humans and great apes. We find that genes with alterations of promoter methylation tend to show increased rates of divergence in their protein sequence, and in contrast we also identify many genes with regulatory changes between human and chimpanzee that have perfectly conserved protein sequence. Our study provides the first global view of evolutionary epigenetic changes that have occurred in the genomes of all species of great apes.
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影响因子：
4.3
作者：
Eden E;Lipson D;Yogev S;Yakhini Z
通讯作者：
Yakhini Z
影响因子：
3.5
作者：
Dal Zotto, L;Quaderi, NA;Rugarli, EI
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Rugarli, EI
影响因子：
7
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Gordon L;Joo JE;Powell JE;Ollikainen M;Novakovic B;Li X;Andronikos R;Cruickshank MN;Conneely KN;Smith AK;Alisch RS;Morley R;Visscher PM;Craig JM;Saffery R
通讯作者：
Saffery R
影响因子：
4.5
作者：
Gertz J;Varley KE;Reddy TE;Bowling KM;Pauli F;Parker SL;Kucera KS;Willard HF;Myers RM
通讯作者：
Myers RM
影响因子：
4.5
作者：
Becquet C;Patterson N;Stone AC;Przeworski M;Reich D
通讯作者：
Reich D