A team of scientists from Baylor College of Medicine, University of Copenhagen, and Centre Nacional d’Anàlisi Genòmica and Centre for Genomic Regulation has discovered fossils of ancient chromosomes in the remains of a woolly mammoth that died 52,000 years ago. The discovery, featured on the cover of Cell, reveals that the structure of these ancient chromosomes is preserved down to the nanometer scale.
“We’ve known that tiny fragments of ancient DNA can survive for long periods of time,” said Dr. Marcela Sandoval-Velasco from the Center for Evolutionary Hologenomics at the University of Copenhagen and co-first author of the study. “But what we found here is a sample where the three-dimensional arrangement of these DNA fragments was frozen in place for tens of millennia, thereby preserving the structure of the whole chromosome.”
Fossil chromosomes offer a new tool for studying life's history because typical ancient DNA fragments are rarely longer than 100 base pairs. In contrast, fossil chromosomes can span hundreds of millions of genetic letters.
“By comparing ancient DNA molecules to the DNA sequences of modern species, it’s possible to find cases where single letters of the genetic code have changed,” said Dr. Olga Dudchenko, assistant professor at Baylor College of Medicine and senior investigator at Rice University. “Fossil chromosomes are a game-changer because knowing the shape makes it possible to assemble entire DNA sequences.”
The research team determined that woolly mammoths had 28 pairs of chromosomes, similar to modern elephants. “It was extremely exciting to be able to count the chromosomes of an extinct creature for the first time,” said Dr. Juan Antonio Rodríguez from University of Copenhagen and Centre Nacional d’Anàlisi Genòmica.
Examining these fossil chromosomes revealed which genes were active due to chromosome compartmentalization – where active and inactive DNA segregates into two spatial neighborhoods inside cell nuclei. This activity pattern often matched modern elephant skin but not always.
“The obvious question for us was: why is it a ‘woolly mammoth’? Why isn’t it a ‘shockingly bald mammoth’?” said Dr. Thomas Gilbert from Center for Hologenomics. The preservation allowed researchers to see key genes regulating hair follicle development with different activity patterns compared to elephants.
The fossilized chromosomes shared many structural features with modern ones, including chromatin loops as small as 50nm in size. “The survival of loops in these ancient chromosomes is perhaps the most impressive part,” said ICREA Research Professor Marc A. Marti-Renom from Centre Nacional d’Anàlisi Genòmica.
To explain how these structures survived intact over millennia despite Einstein's prediction that they shouldn’t exist under ordinary circumstances, researchers posited that chromosome fossils were in a glass-like state resembling molecules in glass.
“Chromoglass is rigid but not an ordered crystal,” explained Dr. Erez Lieberman Aiden from Baylor College and Rice University. "Individual particles or fragments just can’t move very far even after thousands and thousands of years."
Experiments on freeze-dried beef jerky supported this theory by showing how such materials preserve their internal structure despite external forces.
Other contributors include Marianne Dehasque, Claudia Fontsere, Sarah S.T Mak among others listed in full within the publication's funding sources section.
Tom Gilbert and Erez Lieberman Aiden serve as advisors to Colossal Biosciences.
