Scientists have assembled the most complete 3D reconstruction of the woolly mammoth genome, thanks to an incredibly well-preserved specimen that was “freeze-dried” straight after death. With its DNA preserved in a glass-like state, fossilized chromosomes were found for the first time, allowing the team to even see which genes were on and off.
Mammoths and other ice age animals are routinely dragged out of the permafrost in relatively good condition, with their soft tissues preserved. But after many tens of thousands of years – and even as long as a million years – that ancient DNA is usually broken down into small fragments, which makes it hard to reconstruct the puzzle.
Still, scientists have previously managed to sequence the mammoth genome, but that’s only half the picture. The 3D structure of that genome gives a lot of extra information, which would be crucial for work like Colossal’s, a startup that’s planning to resurrect the woolly mammoth within the next decade.
Now, scientists have found a preserved mammoth that retains that 3D structure. Dating back 52,000 years, this large female specimen was dug out of the permafrost in northeastern Siberia in 2018. By sheer luck, it seems the weather effectively freeze-dried this body quickly after the animal’s death, keeping its cellular structure more intact than usual. That resulted in DNA segments up to a million times longer than the fragments found in most ancient samples.
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The researchers took a skin sample from behind the mammoth’s ear, extracted DNA from it, then analyzed it using a method called Hi-C. This technique works by detecting which segments of DNA are physically close together in the cell nucleus, meaning they’re more likely to interact. From this, the 3D structure of the genome can be mapped. Hi-C is already being used to map the human genome.
“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 Marc A. Marti-Renom, corresponding author of the study. “Hi-C allows you to have an approximation of that picture before you start putting the puzzle pieces together.”
Using the genomes of modern elephants as a template, the researchers used Hi-C to create the first 3D map of the mammoth genome. This revealed that mammoths had 28 chromosomes, the same amount as living elephants.
Incredibly, the genome was preserved in such high detail that the team could make out the nanoscale loops that help regulate genes, and even identify which genes were active and inactive in the mammoth’s skin cells. These gene activation patterns were different from those seen in the Asian elephant, which may indicate genes related to its cold tolerance and “woolliness.”
“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,” said Marti-Renom. “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 says the next steps are to look at the gene expression patterns of other tissues in the mammoth. This data could be hugely important for mammoth de-extinction efforts. The technique could also be used on other well-preserved ancient DNA samples, including mummies.
The research was published in the journal Cell.
Source: Cell Press via Scimex
