A Freeze-Dried Mammoth Reveals the Most Complete Ancient Genome in 3D

Scientists have created the most complete 3D reconstruction of the woolly mammoth genome, thanks to a remarkably well-preserved specimen that was “freeze-dried” immediately after death. With its DNA preserved in a glass-like state, they discovered fossilized chromosomes for the first time, enabling them to see which genes were active or inactive.

While mammoths and other ice age animals are frequently well-preserved because of the permafrost shielding their soft tissues, their ancient DNA typically degrades into small fragments over tens of thousands to even a million years, posing challenges for reconstruction efforts.

A New Dimension for Mammoth Resurrection

Scientists have previously managed to sequence the mammoth genome, but that only provides part of the picture.

The 3D structure of the genome offers additional crucial information, especially for projects like Colossal, a startup aiming to resurrect the woolly mammoth within the next decade.

Recently, scientists discovered a preserved mammoth that maintains this 3D structure. This large female specimen, dating back 52,000 years, was excavated from the permafrost in northeastern Siberia in 2018.

By a stroke of luck, the weather quickly freeze-dried the body after death, preserving its cellular structure better than usual.

This preservation resulted in DNA segments up to a million times longer than those typically found in ancient samples.

Mapping the Mammoth Genome in 3D

The researchers took a skin sample from behind the mammoth’s ear, extracted DNA, and analyzed it using a technique called Hi-C.

This method identifies DNA segments that are physically close together in the cell nucleus, indicating they are more likely to interact. This allows the 3D structure of the genome to be mapped. Hi-C is already being used to map the human genome.

“Imagine you have a puzzle with three billion pieces, but you don’t have the picture of the final puzzle to work from,” said Marc A. Marti-Renom, the study’s corresponding author. “Hi-C gives you an approximation of that picture before you start assembling the puzzle pieces.”

Comparative Genomics and 3D Mapping

In fact, using the genomes of modern elephants as a template, the researchers utilized Hi-C to create the first 3D map of the mammoth genome. This revealed that mammoths had 28 chromosomes, the same number as living elephants.

Remarkably, the genome was so well-preserved that the team could identify nanoscale loops that regulate genes and determine which genes were active or inactive in the mammoth’s skin cells.

These gene activation patterns differed from those of the Asian elephant, possibly indicating genes related to 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 in any ancient DNA sample.”

To conclude, the next steps involve examining gene expression patterns in other mammoth tissues. This data could be crucial for mammoth de-extinction efforts. Additionally, the technique could be applied to other well-preserved ancient DNA samples, including mummies.

Read the original article on: New Atlas

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