Topologically associating domains and their role in the evolution of genome structure and function in Drosophila.

Topologically associating domains and their role in the evolution of genome structure and function in Drosophila.
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拓扑相关结构域及其在果蝇基因组结构和功能进化中的作用。

DOI:
10.1101/gr.266130.120
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发表时间:
2021-03
期刊:
影响因子:
7
通讯作者:
Emerson JJ
Emerson JJ
中科院分区:
生物学1区
文献类型:
--
作者:
Liao Y;Zhang X;Chakraborty M;Emerson JJ

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拓扑关联结构域(TADs)最近被确定为三维真核生物基因组组织的基本单位,虽然我们的知识TADs对基因组进化的影响仍然是初步的。为了研究果蝇TADs的分子进化,我们构建了一个新的参考级果蝇基因组组装体和高分辨率的果蝇TADs图谱。伪暗比较D. pseudoobscura和D.黑腹果蝇,这是分开了1.49亿年的分歧,表明他们的基因组中有30%-40%保留保守的TADs。17种果蝇的比较基因组分析显示,染色体重排断点富集在TADs边界,但耗尽。此外,保守的TADs内的基因比位于非保守的TADs内的基因显示出更低的表达差异。此外,我们还发现D. melanogaster(42%)和D. pseudobscura(26%)有自己的TADs,说明转录本的结构可能是决定TADs形成的因素之一。利用14个D. melanogaster strains,与D. simulans物种复合体,和两个obscura分支物种,我们发现的证据,选择作用于SV的边界,但与SV类型之间的选择不同的性质。删除耗尽在分歧和多态性SV,表明纯化选择,而分歧的串联重复富集在边缘相对于多态性,表明它们是适应性的。我们的研究结果强调了TADs在塑造从根本上改变基因组组织的结构突变的获得和保留方面的重要性。
Topologically associating domains (TADs) were recently identified as fundamental units of three-dimensional eukaryotic genomic organization, although our knowledge of the influence of TADs on genome evolution remains preliminary. To study the molecular evolution of TADs in Drosophila species, we constructed a new reference-grade genome assembly and accompanying high-resolution TAD map for D. pseudoobscura. Comparison of D. pseudoobscura and D. melanogaster, which are separated by ∼49 million years of divergence, showed that ∼30%–40% of their genomes retain conserved TADs. Comparative genomic analysis of 17 Drosophila species revealed that chromosomal rearrangement breakpoints are enriched at TAD boundaries but depleted within TADs. Additionally, genes within conserved TADs show lower expression divergence than those located in nonconserved TADs. Furthermore, we found that a substantial proportion of long genes (>50 kbp) in D. melanogaster (42%) and D. pseudoobscura (26%) constitute their own TADs, implying transcript structure may be one of the deterministic factors for TAD formation. By using structural variants (SVs) identified from 14 D. melanogaster strains, its three closest sibling species from the D. simulans species complex, and two obscura clade species, we uncovered evidence of selection acting on SVs at TAD boundaries, but with the nature of selection differing between SV types. Deletions are depleted at TAD boundaries in both divergent and polymorphic SVs, suggesting purifying selection, whereas divergent tandem duplications are enriched at TAD boundaries relative to polymorphism, suggesting they are adaptive. Our findings highlight how important TADs are in shaping the acquisition and retention of structural mutations that fundamentally alter genome organization.
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