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Human "jumping genes" caught in action !

Throughout evolution, the genome of most living beings has become more complex due to transposable elements or "jumping genes", DNA fragments that move or duplicate from one place on a chromosome to another. Researchers from Inserm, CNRS, Université Côte d'Azur and the University of Montpellier were able to capture these "jumping genes" right after they had moved and compared their observations with already existing databases. Their research, soon to be published in Molecular Cell, shows that the integration of "jumping genes" in humans is not random, but could be influenced by certain properties of the genome. These results open up new perspectives in interpreting whole genome sequencing data.

Publication : 04/07/2019
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Transposable elements, also called "jumping genes", are small DNA fragments that can multiply and move in the chromosomes of most living organisms. These genes have proliferated so much in mammals and primates that they make up more than half of our chromosomes! Of course, they do not all jump at the same time, in all our cells. Among all the copies present in our DNA, only a small fraction are constantly active. All the others are molecular vestiges that reflect millions of years of evolution during which harmful insertions were eliminated and beneficial ones preserved.

In humans, the most active jumping genes are L1 retrotransposons. By jumping, they can alter or destroy genes and cause genetic diseases, such as hemophilia or muscular dystrophy. L1 retrotransposons are also particularly active in some forms of cancer, and may be involved in cellular aging or in certain mental illnesses.

Do L1 retrotransposons target specific chromosomal regions or is their insertion random? The teams of Gaël Cristofari and Simona Saccani, INSERM Research Directors at the Institute for Research on Cancer and Aging in Nice - Ircan (Inserm, CNRS, Université Côte d'Azur), and their collaborators at the University of Montpellier, have managed to capture these jumping genes in action immediately after they had jumped to a new position, using a "high-throughput" genome sequencing technique. By comparing their observations with genomic and epigenomic databases, the researchers identified the genome characteristics that influence the integration of L1 retrotransposons. The main influence is DNA replication, but natural selection after integration also plays a significant role.

Until now, we knew that L1 retrotransposons tended to accumulate in certain areas of our chromosomes, particularly in the heterochromatin. But we did not know if that reflected a particular attraction for these areas, or if they were only tolerated in these areas and eliminated elsewhere by natural selection. Once we determine where they go when they jump and which copies are preserved during evolution, we can discover - in reverse - the areas where they can cause damage,” explains Gaël Cristofari.

These findings improve our understanding of how the jumping genes can cause mutations in humans and contribute to the evolution of our genetic heritage. They could also be useful in the future to interpret whole genome sequencing data, particularly in personalized medicine or in major sequencing programs.
This work could not be possible without the support of the Foundation for Medical Research, the PACA Cancéropôle, the European Council of Research, the French National Research Agency, Labex Signalife, the Research Group on Transposable Elements (CNRS, GDR 3546), the FHU OncoAge, and the European Erasmus Mundus Mobility with Asia program.

Communiqué Inserm