Scientists from Baylor College of Medicine and other institutions have announced the discovery of ancient chromosome subfossils in a female mammoth fossil.Mammutus primigeniusThe mammoth, a species of mammoth known as the pygmy mammoth, died 52,000 years ago in what is now Siberia. The fossil preserves the structure of its ancient chromosomes down to the nanometer (billionth of a meter) scale. Researchers hypothesize that the cold of Siberia naturally freeze-dried the mammoth's skin, causing a glass transition that preserved the fossil.
Sandoval Velasco othersAssembled the genome and 3D chromosome structure of a 52,000-year-old woolly mammoth. Image courtesy of Sandoval Velasco. others., doi: 10.1016/j.cell.2024.06.002.
“This is a new type of fossil, one whose scale far exceeds that of individual ancient DNA fragments, with sequences a million times larger,” said Dr. Erez Lieberman Aiden, director of the Center for Genome Architecture at Baylor College of Medicine.
“This is also the first time that an ancient sample has been karyotyped.”
Knowing the three-dimensional structure of a genome gives us a lot of additional information beyond its sequence, but most ancient DNA specimens are made up of very small, jumbled up pieces of DNA.
Building on their work mapping the 3D structure of the human genome, Dr Aiden and his colleagues reasoned that the same strategy could be used to assemble ancient genomes, provided suitable ancient DNA samples were found.
The researchers tested dozens of samples over a five-year period, eventually locating an unusually well-preserved woolly mammoth that was unearthed in September 2018 near Belaya Gora, in the Sakha Republic in northeastern Siberia.
“We believe that the freeze-drying occurred naturally shortly after death, and the nuclear structures in the dried samples can remain viable for an incredibly long period of time,” said Dr. Olga Dudchenko of the Center for Genome Structure at Baylor College of Medicine.
To reconstruct the mammoth's genome structure, the authors extracted DNA from skin samples taken from behind the mammoth's ears.
They are, High C This allows them to detect which parts of DNA are in spatial proximity and likely to interact in their natural state within the nucleus.
“Imagine having a puzzle with 3 billion pieces, but not having the final puzzle picture at hand,” said Professor Marc-Marty-Renom, a structural genomicist at the National Center for Genome Analysis and Genomic Regulation.
“Hi-C allows me to get a rough idea of ​​what the picture looks like before I start putting the puzzle pieces together.”
They then combined the physical information from the Hi-C analysis with DNA sequences to identify interacting DNA sections and produced a neat map of the mammoth genome using the modern elephant genome as a template.
The analysis revealed that mammoths had 28 chromosomes, the same number as modern Asian and African elephants.
Remarkably, the fossilized mammoth chromosomes retained a great deal of physical integrity and detail, including the nanoscale loops that contact transcription factors with the genes they control.
By examining the compartmentalization of genes within the nucleus, the scientists were able to identify active and inactive genes in the mammoth skin cells, a proxy for epigenetics and transcriptomics.
Compared with skin cells from the mammoth's closest relative, the Asian elephant, the mammoth's skin cells showed different gene activation patterns, including genes that may be related to fur and cold tolerance.
“For the first time we have mammoth tissue where we can roughly tell which genes are on and which are off,” said Professor Martti Renom.
“This is a surprising new type of data, the first time we've measured cell-specific genetic activity of genes in ancient DNA samples.”
Team result Published in today's journal cell.
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Marcela Sandoval Velasco others2024. A 52,000-year-old mammoth skin sample contains 3D genome structure. cell 187(14):3541-3562; doi:10.1016/j.cell.2024.06.002
Source: www.sci.news
