Programmed DNA elimination in the parasitic nematode Ascaris.

Programmed DNA elimination in the parasitic nematode Ascaris.
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寄生线虫Ascaris中的编程DNA消除。

DOI:
10.1371/journal.ppat.1011087
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发表时间:
2023-03
期刊:
影响因子:
6.7
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
作者:

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在大多数生物体中,整个基因组在整个生命周期中保持不变。然而,在一些物种中也有例外,它们的基因组在发育过程中通过一种称为程序性DNA消除(PDE)的过程而减少。在人类和猪寄生虫蛔虫中,PDE发生在胚胎发生的第4至16个细胞阶段,此时种系染色体片段化,所有体细胞中特异性DNA序列可重复丢失。早在120多年前,人们就在蛔虫中发现了PDE,但直到最近才对其分子细节有所了解。基因组测序显示,蛔虫大约有1000个生殖系表达基因被消除,这表明PDE是一种基因沉默机制。在PDE期间,所有种系染色体末端都被移除和重塑。此外,PDE通过分裂许多种系染色体来增加体细胞基因组中染色体的数量。比较基因组学表明,这些种系染色体产生于融合事件。PDE在融合位点分离这些染色体。这些结果表明PDE在染色体核型和进化中起着重要作用。此外,通过对其他寄生性和自由寄生性线虫PDE的比较分析,揭示了PDE的保守性,提示其具有重要的生物学意义。我们总结了蛔虫及其近缘种PDE的已知情况。我们还讨论了PDE在人类和动物寄生虫中的其他潜在功能、机制和演化。
In most organisms, the whole genome is maintained throughout the life span. However, exceptions occur in some species where the genome is reduced during development through a process known as programmed DNA elimination (PDE). In the human and pig parasite Ascaris, PDE occurs during the 4 to 16 cell stages of embryogenesis, when germline chromosomes are fragmented and specific DNA sequences are reproducibly lost in all somatic cells. PDE was identified in Ascaris over 120 years ago, but little was known about its molecular details until recently. Genome sequencing revealed that approximately 1,000 germline-expressed genes are eliminated in Ascaris, suggesting PDE is a gene silencing mechanism. All germline chromosome ends are removed and remodeled during PDE. In addition, PDE increases the number of chromosomes in the somatic genome by splitting many germline chromosomes. Comparative genomics indicates that these germline chromosomes arose from fusion events. PDE separates these chromosomes at the fusion sites. These observations indicate that PDE plays a role in chromosome karyotype and evolution. Furthermore, comparative analysis of PDE in other parasitic and free-living nematodes illustrates conserved features of PDE, suggesting it has important biological significance. We summarize what is known about PDE in Ascaris and its relatives. We also discuss other potential functions, mechanisms, and the evolution of PDE in these parasites of humans and animals of veterinary importance.
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