Nucleosomes shape DNA polymorphism and divergence.
Nucleosomes shape DNA polymorphism and divergence.
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DOI：
10.1371/journal.pgen.1004457
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发表时间：
2014-07
期刊：
影响因子：
4.5
通讯作者：
Langley CH
中科院分区：
文献类型：
--
作者：
Langley SA;Karpen GH;Langley CH
据估计，真核生物中80%的基因组DNA被包装成核小体，核小体与剩余的间隙连接区域一起产生高阶染色质结构。从不同生物中分离的核小体序列在AA、TT和GC二核苷酸频率上表现出~ 10bp的周期性变化。这些序列元素产生内在弯曲的DNA，并帮助建立组蛋白-DNA界面。我们研究了一个关于染色质组织和基因组进化之间相互作用的重要未解问题：高度保守的组蛋白核心固有的DNA序列偏好是否对基因组差异和多态性施加可检测的自然选择？为了解决这一假设，我们从黑腹果蝇胚胎中分离出核体DNA序列，并检查了物种内部和物种之间潜在的基因组变异。我们发现沿黑腹龙谱系的分化在核小体区域是周期性的，碱基随着首选核苷酸的变化而变化，这为核小体相关二核苷酸周期性的产生和维持提供了系统进化力量的新证据。此外，单核苷酸多态性（SNP）频谱在核小体区域显示出惊人的周期性，平行发散模式。优先等位基因在自然种群中出现的频率更高，这与自然选择的核心作用是一致的。这些模式在内含子中的核小体中比在基因间区域中更强，这表明在核小体经历更多位移、重塑和功能修饰的转录区域中选择更强。此外，我们观察到与核小体占用相关的AA/TT二核苷酸的大规模（~ 180bp）周期性富集，而GC二核苷酸的频率峰值出现在连接区域。分化和多态性数据也支持自然选择在这些超核体模式的产生和维持中的作用。我们的研究结果表明，核小体相关的序列周期性处于选择压力下，这意味着核小体和DNA序列之间的结构相互作用影响了序列进化，特别是在内含子中。在真核细胞中，大部分DNA被包装在核小体中，核小体由约147 bp的DNA紧密缠绕在高度保守的组蛋白八聚体上。来自不同生物的核小体DNA显示富at和富gc二核苷酸的反相关~ 10 bp周期性。这些序列特征影响DNA弯曲和形状，促进结构相互作用。我们通过研究与这些基本染色质构建块相关的种间和种内基因组变异，探讨了通过核小体周期性序列偏好介导的自然选择是否塑造了黑腹龙骨非蛋白质编码区的进化。黑腹蛇谱系中核小体结合区域的序列变化反映了观察到的核小体二核苷酸周期。重要的是，我们表明自然种群中多态性的频率在这些区域之间变化，平行分化，优先等位基因的频率更高。这些模式在内含子区最为明显，表明非蛋白质编码区正朝着促进与组蛋白核心规范关联的序列进化。这一结果与DNA和核心之间的相互作用对功能有系统影响的假设是一致的，这些影响是自然选择的结果，而不仅仅是由于突变偏差。这些普遍存在的与组蛋白核心的相互作用部分解释了在未注释的基因组区域观察到的进化限制，并可能导致碱基组成的广泛变化。
An estimated 80% of genomic DNA in eukaryotes is packaged as nucleosomes, which, together with the remaining interstitial linker regions, generate higher order chromatin structures. Nucleosome sequences isolated from diverse organisms exhibit ∼10 bp periodic variations in AA, TT and GC dinucleotide frequencies. These sequence elements generate intrinsically curved DNA and help establish the histone-DNA interface. We investigated an important unanswered question concerning the interplay between chromatin organization and genome evolution: do the DNA sequence preferences inherent to the highly conserved histone core exert detectable natural selection on genomic divergence and polymorphism? To address this hypothesis, we isolated nucleosomal DNA sequences from Drosophila melanogaster embryos and examined the underlying genomic variation within and between species. We found that divergence along the D. melanogaster lineage is periodic across nucleosome regions with base changes following preferred nucleotides, providing new evidence for systematic evolutionary forces in the generation and maintenance of nucleosome-associated dinucleotide periodicities. Further, Single Nucleotide Polymorphism (SNP) frequency spectra show striking periodicities across nucleosomal regions, paralleling divergence patterns. Preferred alleles occur at higher frequencies in natural populations, consistent with a central role for natural selection. These patterns are stronger for nucleosomes in introns than in intergenic regions, suggesting selection is stronger in transcribed regions where nucleosomes undergo more displacement, remodeling and functional modification. In addition, we observe a large-scale (∼180 bp) periodic enrichment of AA/TT dinucleotides associated with nucleosome occupancy, while GC dinucleotide frequency peaks in linker regions. Divergence and polymorphism data also support a role for natural selection in the generation and maintenance of these super-nucleosomal patterns. Our results demonstrate that nucleosome-associated sequence periodicities are under selective pressure, implying that structural interactions between nucleosomes and DNA sequence shape sequence evolution, particularly in introns. In eukaryotic cells, the majority of DNA is packaged in nucleosomes comprised of ∼147 bp of DNA wound tightly around the highly conserved histone octamer. Nucleosomal DNA from diverse organisms shows an anti-correlated ∼10 bp periodicity of AT-rich and GC-rich dinucleotides. These sequence features influence DNA bending and shape, facilitating structural interactions. We asked whether natural selection mediated through the periodic sequence preferences of nucleosomes shapes the evolution of non-protein-coding regions of D. melanogaster by examining the inter- and intra-species genomic variation relative to these fundamental chromatin building blocks. The sequence changes across nucleosome-bound regions on the melanogaster lineage mirror the observed nucleosome dinucleotide periodicities. Importantly, we show that the frequencies of polymorphisms in natural populations vary across these regions, paralleling divergence, with higher frequencies of preferred alleles. These patterns are most evident for intronic regions and indicate that non-protein coding regions are evolving toward sequences that facilitate the canonical association with the histone core. This result is consistent with the hypothesis that interactions between DNA and the core have systematic impacts on function that are subject to natural selection and are not solely due to mutational bias. These ubiquitous interactions with the histone core partially account for the evolutionary constraint observed in unannotated genomic regions, and may drive broad changes in base composition.
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影响因子：
64.8
作者：
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