When it comes to the Ice Age, many people's minds come up with pictures of mammoths walking in long fur. During the period approximately 4.8 to 10000 years ago, the mammoth was one of the most representative organisms. But with the warming of the climate, coupled with slow growth rates, insufficient food, and hunting by humans and predators, the number of mammoths began to rapidly decrease, and the survival rate of young elephants was extremely low, ultimately leading to extinction. The extinction of the entire population of mammoths marked 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 52000 years ago, marking the first time such research has been conducted using ancient DNA samples. This study revealed the organization of the mammoth genome within cells and the expression of specific genes in skin tissues. The relevant achievements have been featured on the cover of the new issue of Cell magazine. This unprecedented research means that resurrecting extinct species may no longer be a dream. Freeze dried chromosome fossils are very precious. Most ancient DNA specimens are composed of very small and "messy" DNA fragments. Eliz Lieberman Eden, director of the Genome Structure Center at Baylor College of Medicine in the United States, believes that based on mapping the three-dimensional structure of the human genome, if the correct ancient DNA samples can be found, that is, samples with intact three-dimensional structures, it is possible to use the same strategy to assemble ancient genomes. The research team tested dozens of samples over a period of approximately 5 years, but progress remains slow. Until 2018, an exceptionally well preserved mammoth was unearthed in northeastern Siberia, Russia. This mammoth was' freeze-dried 'shortly after its death. Due to the fact that the nuclear structure in dehydrated samples can be preserved for a long time, this condition allows DNA to be preserved in a glass like state, avoiding the degradation problem of ancient DNA samples and allowing people today to see unprecedented structural details. The length of mammoth chromosome fossils is millions of times longer than ordinary ancient DNA fragments, representing a completely new type of fossil Aiden said. This mammoth is waiting for people to find it. The team is extremely excited because this time they can gain a deeper understanding of how the mammoth genome is organized within its living cells, as well as which genes are active in the skin tissue from which DNA is extracted. However, 'assembly' remains a challenge. A puzzle of 3 billion pieces needs to be assembled. "Imagine you have a puzzle made up of 3 billion pieces, but it doesn't look like the final piece," said Martin Renom, a structural genomics expert at the National Center for Genetics and Genome Regulation in Barcelona, Spain. Fortunately, "Hi-C technology allows you to have an approximate image before putting the puzzle together. Hi-C is a special method used by the team to reconstruct the genome structure of mammoths. They extracted DNA from skin samples collected behind the ears of mammoths. Hi-C technology enables them to detect which parts of DNA may be very close in space and interact with each other in their natural state in the nucleus. Then, they combined the physical information analyzed by Hi-C with DNA sequencing to identify interacting DNA fragments, and used the genome of today's elephants as a template to create an ordered map of the mammoth genome. Analysis shows that mammoths have 28 chromosomes, which are 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 active and inactive genes within mammoth skin cells - a representative of epigenetics or transcriptomics. The skin cells of mammoths have different gene activation patterns compared to their close relatives, Asian elephants, which may include genes related to their body hair and cold resistance. The method used in this study to explore the infinite possibilities brought by chromosome fossils actually depends on the exceptionally well preserved fossils - the ancient chromosome structures preserved by these fossils have been precise to the nanometer level! But the research team is optimistic that this method can also be used to study other ancient DNA specimens, from mammoths to Egyptian mummies, including museum specimens. Chromosomal fossils undoubtedly become powerful new tools for studying the history of life on Earth. This is because typical ancient DNA fragments rarely exceed 100 base pairs, or 100 "letters" of the genetic code - which is much smaller than the complete DNA sequence of an organism (typically billions of "letters" in length). In contrast, chromosome fossils can span hundreds of millions of genetic "letters". Chromosomal fossils have changed the rules of the game, "said Olga Dudchenko, an assistant professor of molecular and human genetics at Baylor College of Medicine's Center for Genomic Structure." By comparing ancient DNA molecules with the DNA sequences of modern species, it is possible to discover changes in individual 'letters' in the genetic code. In other words, by understanding the shape of chromosomes in living organisms, scientists can assemble the entire DNA sequence of extinct organisms, realizing ideas that were previously impossible. But for now, reviving mammoths is just the beginning. (New Society)