Publication in Nature communications

Birth, expansion, and self-programmed death of endogenous retroviruses in cattle


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Lijing Tang and colleagues (Unit of Animal Genomics) have published an article in Nature Communications, developing a molecular method for quantifying the transposition rate of DNA sequences in bovine semen. Thanks to this method, they have also been able to refine the cycle of endogenous retroviruses.

Half of mammalian genomes are made up of repeated elements ('junk DNA'), the majority of which are transposable elements, i.e. capable of moving within the genome.  Endogenous retroviruses (ERVs) make up around 10% of the genome. These endogenous retroviruses have a life cycle made up of successive stages: an exogenous retrovirus infects an animal, and, on rare occasions, integrates into the germline genome - this is endogenization (birth). From then on, this ERV will be transmitted vertically to descendants, as an integral part of the host genome.  This is followed by the so-called expansion phase, when the young ERV, which has retained the exogenous retrovirus machinery intact, autonomously generates new insertions. Gradually, the ERV ages, accumulates mutations and is repressed by the host, until it can no longer replicate - the end of the cycle. 

In a study published in Nature Communications, Michel Georges and Carole Charlier's team identified a ERV family in cattle, following the observation of a fatal recessive disease, in its expansion phase, i.e. still capable of creating new insertions through a process of retrotransposition and/or reinfection. 

They then developed a molecular method for rigorously quantifying the de novo transposition rate (dnTR) in sperm.  Based on the analysis of sperm from 430 bulls, it was found that this dnTR can vary more than 10-fold from one individual to another, with an average of one new insertion every 150 sperm cells.  Using this dnTR measurement as a quantitative molecular phenotype, a genome-identity association study was carried out.  The researchers identified eight chromosomal regions that influence dnTR.  Fine dissection of these loci revealed that, for four of them, the presence of a polymorphic ERV (not fixed in the population) was directly responsible for an increase in dnTR. 

By analyzing the complete sequence of the 300 polymorphic elements that make up the ERV catalog of the bovine population studied, they found two distinct categories: a category of ERV known as competent (C, 15%), whose machinery is intact, and a category known as defective (D, 85%), having lost its retrotransposition autonomy.  The ERV at the four loci identified by the association study are all competent.  In fact, it is the total number of 'C' alleles (copies) in an individual that is positively correlated with its dnTR, and this explains >25% of the variance in dnTR.  Surprisingly, when we studied the sequence of >3000 de novo insertions, we found that they were predominantly of the 'D' category. 

The researchers therefore concluded that 'D'-type ERVs appear to hijack the 'C'-type ERV machinery for their own benefit, but in so doing, hasten the death of the entire family, like a programmed suicide.

Following this discovery, Lijing Tang, the PhD student who led the study, initiated collaboration with a Swiss team (Dr Etienne Bucher, Agroscope) to apply this method to transposable elements still active in a subset of wheat varieties.

Reference

GWAS reveals determinants of mobilization rate and dynamics of an active endogenous retrovirus of cattle.

Tang L, Swedlund B, Dupont S, Harland C, Costa Monteiro Moreira G, Durkin K, Artesi M, Mullaart E, Sartelet A, Karim L, Coppieters W, Georges M, Charlier C. Nat Commun. 2024 Mar 9;15(1):2154. doi: 10.1038/s41467-024-46434-1

Contacts

Lijing Tang

Carole Charlier

Michel Georges

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