The nematode Oscheius tipulae as a genetic model for programmed DNA elimination.
The nematode Oscheius tipulae as a genetic model for programmed DNA elimination.
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DOI：
10.1016/j.cub.2022.10.043
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发表时间：
2022-12-05
期刊：
影响因子：
9.2
通讯作者：
Wang, Jianbin
中科院分区：
文献类型：
--
作者：
Dockendorff, Thomas C.;Estrem, Brandon;Reed, Jordan;Simmons, James R.;Zadegan, Sobhan Bahrami;Zagoskin, Maxim V.;Terta, Vincent;Villalobos, Eduardo;Seaberry, Erin M.;Wang, Jianbin
程序化DNA消除（PDE）是基因组完整性范式的一个显著例外。在后生动物中，PDE通常与生殖细胞向体细胞分化同时发生。在PDE过程中，部分基因组DNA丢失，导致体细胞基因组减少。先前的研究已经描述了后生动物PDE过程中序列丢失和染色体行为。然而，对于后生动物PDE的机制和后果的研究尚缺乏一个系统。在这里，我们提出了一个功能和遗传模型PDE在自由生活的横纹肌科线虫Oscheius tipulae，一个家庭包括秀丽隐杆线虫。最近有人提出，O. tipulae可以消除DNA。利用分期胚胎和DNA FISH，我们发现O. tipulae PDE发生在胚胎发生的8-16个细胞阶段。我们发现了一个保守的基序，命名为消除序列（Sequence For Elimination， SFE），它适用于6条染色体上所有12个断裂位点，位于保留DNA和消除DNA的交界处。SFE突变体仅在修饰位点表现出“无法消除”的表型。end -seq显示，断裂可以发生在SFE的多个位置，广泛的末端切除后，端粒被添加到保留端和消除端。我们通过野生型胚胎的END-seq、SFE突变体的基因组测序和23个野生分离株的比较基因组学，在染色体末端鉴定了许多功能性SFE。我们建议这些替代的sfe提供了消除序列的灵活性和PDE的故障安全机制。这些研究为研究后生动物PDE的机制和后果建立了一个新的、有吸引力的模型。Dockendorff， Estrem等人对自由生活线虫Oscheius tipulae的遗传和分子分析表明，保守基序在DNA断裂和程序性DNA消除（PDE）的故障安全机制中发挥了重要作用。本研究为研究后生动物PDE的机制和后果建立了一种新的遗传模型。
Programmed DNA elimination (PDE) is a notable exception to the paradigm of genome integrity. In metazoa, PDE often occurs coincident with germline to somatic cell differentiation. During PDE, portions of genomic DNA are lost, resulting in reduced somatic genomes. Prior studies have described the sequences lost and chromosome behavior during metazoan PDE. However, a system for studying the mechanisms and consequences of PDE in metazoa is lacking. Here, we present a functional and genetic model for PDE in the free-living Rhabditidae nematode Oscheius tipulae, a family which includes Caenorhabditis elegans. O. tipulae was recently suggested to eliminate DNA. Using staged embryos and DNA FISH, we show that O. tipulae PDE occurs during embryogenesis at the 8–16 cell stages. We identified a conserved motif, named Sequence For Elimination (SFE), for all 12 break sites on the six chromosomes at the junction of retained and eliminated DNA. SFE mutants exhibit a “fail-to-eliminate” phenotype only at the modified sites. END-seq revealed that breaks can occur at multiple positions within the SFE, with extensive end resection followed by telomere addition to both retained and eliminated ends. We identified many functional SFEs at the chromosome ends through END-seq in the wild-type embryos, genome sequencing of SFE mutants, and comparative genomics of 23 wild isolates. We suggest these alternative SFEs provide flexibility in the sequences eliminated and a fail-safe mechanism for PDE. These studies establish O. tipulae as a new, attractive model to study the mechanisms and consequences of PDE in a metazoan. Genetic and molecular analyses in the free-living nematode Oscheius tipulae by Dockendorff, Estrem, et al. demonstrate an essential role of a conserved motif for DNA break and a fail-safe mechanism for programmed DNA elimination (PDE). This work establishes O. tipulae as a new genetic model to study mechanisms and consequences of PDE in a metazoan.
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发表时间：
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期刊：
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影响因子：
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