Mutational Signatures of Replication Timing and Epigenetic Modification Persist through the Global Divergence of Mutation Spectra across the Great Ape Phylogeny.
Mutational Signatures of Replication Timing and Epigenetic Modification Persist through the Global Divergence of Mutation Spectra across the Great Ape Phylogeny.
复制标题
复制时间和表观遗传修饰的突变特征在整个类人猿系统发育过程中突变谱的全球分歧中持续存在。
DOI：
10.1093/gbe/evab104
复制
发表时间：
2022-01-04
影响因子：
3.3
通讯作者：
Harris K
中科院分区：
文献类型：
--
作者：
Goldberg ME;Harris K
类人猿进化枝表现出不同的三碱基对基因组基序的相对突变率的变化，与密切相关的物种比远亲物种具有更相似的突变谱。这种模式不能用经典的人口统计学或选择力来解释，但意味着DNA复制的保真度在类人猿进化史的每个分支上都以不同的方式受到干扰。在这里，我们使用88种类人猿的全基因组变异来研究这些物种的突变谱是否在整个基因组中存在广泛差异，或者突变谱差异是否是由具有特定功能特征或染色质状态的DNA区室驱动的。我们进行主成分分析（PCA）和突变签名反卷积突变谱确定的功能，包括复制时间和古老的重复内容定义的隔间，找到一致的物种特异性突变签名的证据，不依赖于哪些功能隔间的光谱确定。与此同时，我们发现，许多隔间都有自己的特征突变签名，这些签名在整个类人猿进化史上都是稳定的。例如，在按复制时间划分的突变谱PCA中，解释21.2%变异的第二主成分将所有物种的晚期复制区域与早期复制区域分开。我们的研究结果表明，大猿突变谱进化不是由表观遗传变化驱动的，表观遗传变化改变了特定基因组区域的突变率，而是由反式作用突变修饰剂相当均匀地影响整个基因组的突变。
Great ape clades exhibit variation in the relative mutation rates of different three-base-pair genomic motifs, with closely related species having more similar mutation spectra than distantly related species. This pattern cannot be explained by classical demographic or selective forces, but imply that DNA replication fidelity has been perturbed in different ways on each branch of the great ape phylogeny. Here, we use whole-genome variation from 88 great apes to investigate whether these species’ mutation spectra are broadly differentiated across the entire genome, or whether mutation spectrum differences are driven by DNA compartments that have particular functional features or chromatin states. We perform principal component analysis (PCA) and mutational signature deconvolution on mutation spectra ascertained from compartments defined by features including replication timing and ancient repeat content, finding evidence for consistent species-specific mutational signatures that do not depend on which functional compartments the spectra are ascertained from. At the same time, we find that many compartments have their own characteristic mutational signatures that appear stable across the great ape phylogeny. For example, in a mutation spectrum PCA compartmentalized by replication timing, the second principal component explaining 21.2% of variation separates all species’ late-replicating regions from their early-replicating regions. Our results suggest that great ape mutation spectrum evolution is not driven by epigenetic changes that modify mutation rates in specific genomic regions, but instead by trans-acting mutational modifiers that affect mutagenesis across the whole genome fairly uniformly.
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DOI：
10.1073/pnas.1900714116
发表时间：
2019-09-03
影响因子：
11.1
作者：
Agarwal, Ipsita;Przeworski, Molly
通讯作者：
Przeworski, Molly
DOI：
10.1073/pnas.1418652112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Harris, Kelley
通讯作者：
Harris, Kelley
影响因子：
9.8
作者：
Harr, Bettina;Karakoc, Emre;Neme, Rafik;Teschke, Meike;Pfeifle, Christine;Pezer, Zeljka;Babiker, Hiba;Linnenbrink, Miriam;Montero, Inka;Scavetta, Rick;Abai, Mohammad Reza;Puente Molins, Marta;Schlegel, Mathias;Ulrich, Rainer G.;Altmueller, Janine;Franitza, Marek;Buentge, Anna;Kuenzel, Sven;Tautz, Diethard
通讯作者：
Tautz, Diethard
影响因子：
16
作者：
Harris, RS;Petersen-Mahrt, SK;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
12.3
作者：
Ananda G;Chiaromonte F;Makova KD
通讯作者：
Makova KD