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人类病原体中功能性同源物的水平基因转移

Horizontal gene transfer of a functional homolog in the human pathogen .

作者信息

Wendt George, Collins James J

机构信息

Department of Pharmacology, University of Texas Southwestern Medical Center.

出版信息

bioRxiv. 2024 May 27:2024.05.27.596073. doi: 10.1101/2024.05.27.596073.

Abstract

Schistosomes are parasitic flatworms responsible for the neglected tropical disease schistosomiasis, causing devastating morbidity and mortality in the developing world. The parasites are protected by a skin-like tegument, and maintenance of this tegument is controlled by a schistosome ortholog of the tumor suppressor TP53. To understand mechanistically how controls tegument production, we identified a cyclin dependent kinase inhibitor homolog () that was co-expressed with . RNA interference of resulted in a hyperproliferation phenotype, that, in combination with RNA interference yielded abundant tumor-like growths, indicating that and are bona fide tumor suppressors in . Interestingly, homologs are widely present throughout parasitic flatworms but evidently absent from their free-living ancestors, suggesting this cki homolog came from an ancient horizontal gene transfer event. This in turn implies that the evolution of parasitism in flatworms may have been aided by a highly unusual means of metazoan genetic inheritance.

摘要

血吸虫是寄生扁虫,可引发被忽视的热带疾病血吸虫病,在发展中世界造成毁灭性的发病和死亡。这些寄生虫由类似皮肤的被膜保护,而这种被膜的维持由肿瘤抑制因子TP53的血吸虫直系同源物控制。为了从机制上理解 如何控制被膜产生,我们鉴定出一种与 共表达的细胞周期蛋白依赖性激酶抑制剂同源物()。对 的RNA干扰导致了过度增殖表型,与对 的RNA干扰相结合产生了大量肿瘤样生长物,表明 和 是 中的真正肿瘤抑制因子。有趣的是, 同源物广泛存在于整个寄生扁虫中,但在它们自由生活的祖先中显然不存在,这表明这种cki同源物来自一个古老的水平基因转移事件。这反过来意味着扁虫寄生现象的进化可能得到了一种非常不寻常的后生动物遗传方式的帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f4/11160599/a26324a480e3/nihpp-2024.05.27.596073v1-f0001.jpg

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