By Stephen Beech via SWNS
The resurrection of woolly mammoths is a major step closer after the first ever 3D reconstruction of 52,000-year-old chromosomes – from a “freeze-dried” carcass.
Scientists say the “unprecedented” breakthrough was only possible because the now extinct beast underwent “freeze-drying” shortly after it died in Siberia tens of thousands of years ago – meaning its DNA was preserved in a “glass-like” state.
An international research team assembled the genome and 3D chromosomal structures of the mammoth – the first time such a feat has been achieved for any ancient DNA sample.
They say the fossilized chromosomes, which are around a million times longer than most ancient DNA fragments, provide insight into how the mammoth’s genome was organized within its living cells and which genes were active within the skin tissue from which the DNA was extracted.
Study corresponding author Professor Erez Lieberman Aiden, of Baylor College of Medicine, said: “This is a new type of fossil, and its scale dwarfs that of individual ancient DNA fragments – a million times more sequence.
“It is also the first time a karyotype of any sort has been determined for an ancient sample.”
He explained that knowing the three-dimensional architecture of a genome provides a lot of extra 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, Aiden thought that if the right ancient DNA sample could be found – one with the 3D organization of the fragments still intact – it would be possible to use the same strategies to assemble ancient genomes.
The international research team, whose findings were published in the journal Cell, tested dozens of samples over the course of five years before landing on an “unusually well-preserved” woolly mammoth that was excavated in northeastern Siberia in 2018.
Study co-author Dr. Olga Dudchenko, also of Baylor College of Medicine, said: “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.”
To reconstruct the mammoth’s genomic architecture, the research team extracted DNA from a skin sample taken from behind the mammoth’s ear.
The researchers 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.
Co-author Professor Marc Marti-Renom, of the Centre for Genomic Regulation (CRG) in Barcelona, Spain, said: “Imagine you have a puzzle that has three billion pieces, but you don’t have the picture of the final puzzle to work from.
“Hi-C allows you to have an approximation of that picture before you start putting the puzzle pieces together.”
The research team 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.
Their analysis revealed that woolly mammoths had 28 chromosomes – the same number as present-day Asian and African elephants.
The team said that “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.
The researchers were able to identify genes that were active and inactive within the mammoth’s skin cells – a proxy for epigenetics or transcriptomics.
They found that 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.
Marti-Renom said: “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.”
He added: “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 researchers are optimistic that the same method could be used to study other ancient DNA specimens -from mammoths to Egyptian mummies – as well as more recently preserved museum specimens.
Co-author Professor Thomas Gilbert, of the University of Copenhagen, Denmark, added: “These results have obvious consequences for contemporary efforts aimed at woolly mammoth de-extinction.”
