Scientists from Baylor College of Medicine and elsewhere say they have discovered subfossils of ancient chromosomes in the remains of a female woolly mammoth (Mammuthus primigenius) that died 52,000 years ago in what is now Siberia. The fossils preserve the structure of the ancient chromosomes down to the nanometer scale — billionths of a meter. The researchers hypothesize that the mammoth skin spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved the fossils.
Sandoval-Velasco et al. assembled the genome and 3D chromosomal structures of a 52,000-year-old woolly mammoth. Image credit: Sandoval-Velasco et al., doi: 10.1016/j.cell.2024.06.002.
“This is a new type of fossil, and its scale dwarfs that of individual ancient DNA fragments — a million times more sequence,” said Dr. Erez Lieberman Aiden, director of the Center for Genome Architecture at Baylor College of Medicine.
“It is also the first time a karyotype of any sort has been determined for an ancient sample.”
Knowing the three-dimensional architecture of a genome provides a lot of additional information beyond its sequence, but most ancient DNA specimens consist of very small, scrambled DNA fragments.
Building off work mapping the 3D structure of the human genome, Dr. Aiden and colleagues thought that if the right ancient DNA sample could be found — it would be possible to use the same strategies to assemble ancient genomes.
They tested dozens of samples over the course of five years before landing on an unusually well-preserved woolly mammoth that was excavated near Belaya Gora, Sakha Republic, northeastern Siberia in September 2018.
“We think it spontaneously freeze-dried shortly after its death. The nuclear architecture in a dehydrated sample can survive for an incredibly long period of time,” said Dr. Olga Dudchenko, also from the Center for Genome Architecture at Baylor College of Medicine.
To reconstruct the mammoth’s genomic architecture, the authors extracted DNA from a skin sample taken behind the mammoth’s ear.
They used a method called Hi-C that allows them to detect which sections of DNA are likely to be in close spatial proximity and interact with each other in their natural state in the nucleus.
“Imagine you have a puzzle that has three billion pieces, but you don’t have the picture of the final puzzle to work from,” said Professor Marc Marti-Renom, a structural genomicist at the Centre Nacional d’Anàlisi Genòmica and the Centre for Genomic Regulation.
“Hi-C allows you to have an approximation of that picture before you start putting the puzzle pieces together.”
Then, they combined the physical information from the Hi-C analysis with DNA sequencing to identify the interacting DNA sections and create an ordered map of the mammoth’s genome, using the genomes of present-day elephants as a template.
The analysis revealed that woolly mammoths had 28 chromosomes — the same number as present-day Asian and African elephants.
Remarkably, the fossilized mammoth chromosomes also retained a huge amount of physical integrity and detail, including the nanoscale loops that bring transcription factors in contact with the genes they control.
By examining the compartmentalization of genes within the nucleus, the scientists were able to identify genes that were active and inactive within the mammoth’s skin cells — a proxy for epigenetics or transcriptomics.
The mammoth skin cells had distinct gene activation patterns compared to the skin cells of its closest relative, the Asian elephant, including for genes potentially related to its woolly-ness and cold tolerance.
“For the first time, we have a woolly mammoth tissue for which we know roughly which genes were switched on and which genes were off,” Professor Marti-Renom said.
“This is an extraordinary new type of data, and it’s the first measure of cell-specific gene activity of the genes in any ancient DNA sample.”
The team’s results appear today in the journal Cell.
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Marcela Sandoval-Velasco et al. 2024. Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample. Cell 187 (14): 3541-3562; doi: 10.1016/j.cell.2024.06.002
Source : Breaking Science News