3D reconstruction of woolly mammoth genome from 'fossil' chromosomes

3D reconstruction of woolly mammoth genome from 'fossil' chromosomes

This story begins fifty-two thousand years ago. A mammoth died in what is now Siberia. Its body froze almost instantly in the temperatures of the last Ice Age.

Back in 2020, in front of a computer, in a lab in Barcelona, “A few days before the world shut down [en raison de la pandémie de Covid-19] », In the words of paleogeneticist Marcela Sandoval Velasco, co-first author of the innovative study, Posted Thursday, July 11 In the scientific journal cellOn that day, for the first time, the computer echoed. “fossil chromosomes”. “They were able to reconstruct the chromosomes. This is a huge step forward!”“It's a very exciting time,” says Eva-Maria Geigl, a paleontologist at the Jacques Monod Institute in Paris, who was not involved in the study.

To achieve this feat, it took ten years of scientific adventure that brought together two families of geneticists: paleogenomicists, who analyze ancient DNA, and structural genomicists. The latter study the structure of the genome. In the nucleus of our cells, chromosomes, made up of DNA and proteins, do not fold randomly. Proximate regions interact physically with each other, even though they may be very far apart in genetic sequence. Like two distant chapters in a book that make up the genome, they are brought together by the reader who turns the pages separating them. Knowing the three-dimensional structure of the genome is enough to get a picture Gene activity »“This is a very important finding,” says Marc Martí Renommé, a structural genomics researcher at the National Center for Genomic Analysis in Barcelona and co-author of the study.

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Until now, paleontologists have been stuck in the linear dimension. Because ancient DNA usually appears in small fragments. And its analysis It consists of observing differences in genetic sequence and mutations. “What mutations tell you is what your genome can do, but it doesn't tell you what it does.”Régis Debruyne, paleontology research engineer at the National Museum of Natural History in Paris, explains.

Artist's impression of one of the last woolly mammoths on Wrangel Island in the Arctic Ocean, off the coast of Siberia.

But the authors of this study had a hunch: the three-dimensional structure of chromosomes could be preserved in some cases. And it was this mammoth, found in permafrost, this permanently frozen ground, by a scientific expedition in 2018, that made it possible to confirm this.

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