Huang Junhong, Chen Zhirong, Li Bin, Qu Lianghu, Yang Jianhua
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China.
The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
Adv Biotechnol (Singap). 2023 Oct 31;1(4):5. doi: 10.1007/s44307-023-00005-5.
Retrotransposons are highly prevalent in most animals and account for more than 35% of the human genome. However, the prevalence, biogenesis mechanism and function of retrotransposons remain largely unknown. Here, we developed retroSeeker, a novel computational software that identifies novel retrotransposons from pairwise alignments of genomes and decodes their biogenesis, expression, evolution and potential functions. We discovered that the majority of new retrotransposons exhibit a specific L1 endonuclease cleavage motif, with some motifs precisely located ten nucleotides upstream of the insertion site. We identified that a large number of candidate functional genes might be generated through a retrotransposition mechanism. Importantly, we uncovered previously uncharacterized classes of retrotransposons related to histone genes, mitochondrial genes and vault RNAs. Moreover, we elucidated the tissue-specific expression of retrotransposons and demonstrated their ubiquitous expression in various cancer types. We also revealed the complex evolutionary patterns of retrotransposons and identified numerous species-specific retrotransposition events. Taken together, our findings establish a paradigm for discovering novel classes of retrotransposons and elucidating their new characteristics in any species.
逆转录转座子在大多数动物中高度普遍，占人类基因组的35%以上。然而，逆转录转座子的普遍性、生物发生机制和功能在很大程度上仍不清楚。在这里，我们开发了retroSeeker，这是一种新型计算软件，可从基因组的成对比对中识别新型逆转录转座子，并解码它们的生物发生、表达、进化和潜在功能。我们发现，大多数新的逆转录转座子表现出特定的L1内切酶切割基序，其中一些基序精确地位于插入位点上游十个核苷酸处。我们确定，大量候选功能基因可能通过逆转座机制产生。重要的是，我们发现了以前未表征的与组蛋白基因、线粒体基因和穹窿体RNA相关的逆转录转座子类。此外，我们阐明了逆转录转座子的组织特异性表达，并证明了它们在各种癌症类型中的普遍表达。我们还揭示了逆转录转座子复杂的进化模式，并确定了许多物种特异性的逆转座事件。综上所述，我们的研究结果为发现新型逆转录转座子类并阐明其在任何物种中的新特征建立了一个范例。
