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When talking about the Ice Age, many people will think of mammoths with long hair and marching forward. In the period between about 4.8 million and 10,000 years ago, mammoths were one of the most representative creatures. However, as the climate warmed, coupled with factors such as slow growth, lack of food, and hunting by humans and wild animals, the number of mammoths began to decrease rapidly, the survival rate of young mammoths was extremely low, and eventually they became extinct.

The extinction of the entire mammoth population heralded the end of an ice age.

Now, an international research team has successfully reconstructed the genome and three-dimensional chromosome structure of a mammoth that lived 52,000 years ago. This is the first time such research has been conducted using ancient DNA samples. The study revealed how the mammoth genome was organized in cells and how specific genes were expressed in skin tissue. The relevant results appear on the cover of the latest issue of Cell magazine.

This unprecedented research means that resurrecting extinct creatures may no longer be a dream.

"Freeze-dried" chromosome fossils are very valuable

Most ancient DNA samples are composed of very small and "messy" DNA fragments. Elize Lieberman Eden, director of the Genome Structure Center at Baylor College of Medicine in the United States, believes that if the correct ancient DNA sample can be found, that is, a sample with a still intact three-dimensional structure, it is possible to use the same strategy to assemble the ancient genome based on the mapping of the three-dimensional structure of the human genome.

The research team tested dozens of samples over about five years, but progress was slow.

Until 2018, a mammoth in exceptionally good condition was unearthed in northeastern Siberia, Russia. The mammoth was "freeze-dried" shortly after death. Since the nuclear structure in the dehydrated sample can be preserved for a long time, this condition allows the DNA to be preserved in a glass-like state, avoiding the degradation problem of ancient DNA samples in the past, and allowing people today to see unprecedented structural details.

"The mammoth chromosome fossils are millions of times longer than ordinary ancient DNA fragments and represent a completely new type of fossil," said Aiden.

The mammoth is waiting to be found. The team is excited because it will give them a deeper understanding of how the mammoth genome is organized in its living cells and which genes are active in the skin tissue from which the DNA was extracted. However, "assembly" is still a difficult problem.

A puzzle of 3 billion pieces needs to be assembled

"Imagine that you have a puzzle made up of 3 billion pieces, but you don't have the final look of the puzzle." Fortunately, "Hi-C technology allows you to have an approximate image before you put the puzzle together," said Martin Renom, a structural genomicist at the National Center for Genomics and Center for Genomic Regulation in Barcelona, ​​Spain. Hi-C is a special method used by the team to reconstruct the genome structure of the mammoth. They extracted DNA from skin samples collected from behind the mammoth's ears. Hi-C technology allows them to detect which parts of the DNA may be very close in space and interact with each other in their natural state in the cell nucleus.

They then combined the physical information from the Hi-C analysis with DNA sequencing to identify interacting DNA segments and used the genome of today's elephants as a template to create an ordered map of the mammoth genome. The analysis showed that mammoths had 28 chromosomes, the same as today's Asian and African elephants.

By examining the compartmentalization of genes within the cell nucleus, the team was able to identify which genes were active and which were inactive within mammoth skin cells—a proxy for epigenetics, or transcriptomics. Mammoth skin cells had different patterns of gene activation than skin cells from their closest relative, the Asian elephant, which may include genes related to their body hair and cold tolerance.

Chromosome fossils offer endless possibilities

The method used in this study depends on an exceptionally well-preserved fossil that preserves the ancient chromosome structure down to the nanometer scale, but the team is optimistic that the method could be used to study other ancient DNA specimens, from mammoths to Egyptian mummies, including museum specimens.

Chromosome fossils have undoubtedly become a powerful new tool for studying the history of life on Earth. This is because a typical ancient DNA fragment rarely exceeds 100 base pairs, or 100 "letters" of the genetic code - which is much smaller than the complete DNA sequence of an organism (usually billions of "letters" long). In contrast, chromosome fossils can span hundreds of millions of genetic "letters".

"Chromosome fossils are a game changer," said Olga Dudchenko, assistant professor of molecular and human genetics at the Center for Genome Architecture at Baylor College of Medicine, because "by comparing ancient DNA molecules with DNA sequences of modern species, it is possible to detect changes in single 'letters' in the genetic code."

In other words, by understanding the shape of an organism's chromosomes, scientists can assemble the entire DNA sequence of an extinct creature, making possible ideas that were previously impossible.

But for now, resurrecting the mammoth is just the beginning.

Column Editor: Qin Hong Text Editor: Da Xi Title Image Source: Tuchong Image Editor: Cao Liyuan

Source: Author: Science and Technology Daily