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GWAS reveals determinants of mobilization rate and dynamics of an active endogenous retrovirus of cattle
Nature Communications ( IF 14.7 ) Pub Date : 2024-03-09 , DOI: 10.1038/s41467-024-46434-1
Lijing Tang 1 , Benjamin Swedlund 1, 2 , Sébastien Dupont 1 , Chad Harland 1, 3 , Gabriel Costa Monteiro Moreira 1 , Keith Durkin 1, 4 , Maria Artesi 1, 4 , Eric Mullaart 5 , Arnaud Sartelet 1, 6 , Latifa Karim 1, 7 , Wouter Coppieters 1, 7 , Michel Georges 1 , Carole Charlier 1
Affiliation  

Five to ten percent of mammalian genomes is occupied by multiple clades of endogenous retroviruses (ERVs), that may count thousands of members. New ERV clades arise by retroviral infection of the germline followed by expansion by reinfection and/or retrotransposition. ERV mobilization is a source of deleterious variation, driving the emergence of ERV silencing mechanisms, leaving “DNA fossils”. Here we show that the ERVK[2-1-LTR] clade is still active in the bovine and a source of disease-causing alleles. We develop a method to measure the rate of ERVK[2-1-LTR] mobilization, finding an average of 1 per ~150 sperm cells, with >10-fold difference between animals. We perform a genome-wide association study and identify eight loci affecting ERVK[2-1-LTR] mobilization. We provide evidence that polymorphic ERVK[2-1-LTR] elements in four of these loci cause the association. We generate a catalogue of full length ERVK[2-1-LTR] elements, and show that it comprises 15% of C-type autonomous elements, and 85% of D-type non-autonomous elements lacking functional genes. We show that >25% of the variance of mobilization rate is determined by the number of C-type elements, yet that de novo insertions are dominated by D-type elements. We propose that D-type elements act as parasite-of-parasite gene drives that may contribute to the observed demise of ERV elements.



中文翻译:


GWAS揭示了牛活性内源逆转录病毒的动员率和动态的决定因素



哺乳动物基因组的 5% 到 10% 被内源逆转录病毒 (ERV) 的多个分支占据,这些分支可能有数千个成员。新的 ERV 进化枝是由种系逆转录病毒感染随后通过再感染和/或逆转录转座进行扩增而产生的。 ERV动员是有害变异的一个来源,推动ERV沉默机制的出现,留下“DNA化石”。在这里,我们表明 ERVK[2-1-LTR] 进化枝在牛体内仍然活跃,并且是致病等位基因的来源。我们开发了一种测量 ERVK[2-1-LTR] 动员率的方法,发现平均每约 150 个精子细胞有 1 个,动物之间的差异超过 10 倍。我们进行了全基因组关联研究,并确定了影响 ERVK[2-1-LTR] 动员的八个位点。我们提供的证据表明,其中四个基因座中的多态性 ERVK[2-1-LTR] 元件导致了这种关联。我们生成了全长 ERVK[2-1-LTR] 元件的目录,并表明它包含 15% 的C型自主元件和 85% 的缺乏功能基因的D型非自主元件。我们表明,>25% 的动员率方差是由C型元件的数量决定的,但从头插入主要由D型元件主导。我们提出, D型元件充当寄生虫的寄生虫基因驱动器,可能有助于观察到的 ERV 元件的消亡。

更新日期:2024-03-11
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