Stunning 3D chromosomes in frozen mammoths may help resurrect the beasts
The first sign that Erez Lieberman Aiden and his team were onto something special was the ice age beast’s hairdo. Woolly mammoth hides that froze, thawed, and refroze tend to go bald.
But the mammoth that had perished some 52,000 years ago in Siberia had retained a tangle of chestnut-brown hair over much of its body, suggesting it had stayed frozen since the animal died.
The closer the scientists peered, the more wonders they beheld. A microscope revealed the mammoth’s hair follicles. Looking even closer, they saw loops of chromatin—the DNA and proteins that make up chromosomes—preserved in a glasslike state in which the molecules are packed tightly.
From that exquisite slab of skin, the researchers assembled the mammoth’s genome and the 3D architecture of its chromosomes. The structure closely resembles that of modern elephants and showed the genome in action, revealing clues to which genes were active in mammoth skin, as Aiden, director of the Center for Genome Architecture at Baylor College of Medicine (BCM), and colleagues report in the 11 July issue of Cell. “This is a fantastic result that has the potential to become a real milestone,” says Michael Hofreiter, an evolutionary geneticist at the University of Potsdam who was not involved in the study.
Knowing the structure of the mammoth genome may put wind in the sails of controversial efforts to resurrect the beast. More generally, Hofreiter says, the results could “move research on extinct species forward in ways we long wanted.” “The next big forefront in the field will come from novel chemistry to unlock deeper time fossils,” older than 1 million years, adds Hendrik Poinar, an evolutionary geneticist at McMaster University who also was not involved in the study.
Chromatin glass, or “chromoglass,” as the researchers call it, can form in tissues that have been desiccated like beef jerky, says co-author Marc Martí-Renom, a structural geneticist at the Spanish National Center for Genomic Analysis (CNAG). “We believe dehydration is the key element here,” not temperature, he says. Such desiccation may have occurred in other remains in Siberia’s vast permafrost meat locker, and perhaps in nonfrozen remains such as Egyptian mummies.
HUNT FOR MAMMOTH CHROMOSOMES
The hunt for long-lost chromosomes began a decade ago, when Aiden, along with BCM’s Olga Dudchenko and Tom Gilbert of the University of Copenhagen, sought to apply to ancient DNA a technique called Hi-C that Aiden had helped pioneer. Hi-C offers a way to sequence genomes in 3D.
Love Dalén, an evolutionary geneticist at the Centre for Palaeogenetics in Stockholm, studied a chestnut-haired mammoth that Russian scientists excavated in Siberia in 2018. The team also studied samples from another mammoth, which has been hailed as the best preserved specimen ever: a young female nicknamed Yuka, found near the Laptev Sea in 2010 by local Yukagirs. Together the two mammoths revealed “a new type of fossil,” that preserves 3D structure and long strings of DNA, Aiden says: “Fossil chromosomes that span a million–fold more sequence than typical ancient DNA fragments.”
The results confirm that mammoths, like modern elephants, had 28 chromosomes. The genomes have “nearly identical” structures, Gilbert says. “Boring for us, but great for the de-extinction people.” For example, the biotech firm Colossal Biosciences is planning to splice quintessential mammoth genes into the elephant genome—a task made easier by the kissing-cousin chromosomes—and then use modern elephants as surrogate mothers to give birth to a mammothlike creature.
What’s more, genome architecture “tells you a heck of a lot about function,” Aiden says. “We can figure out which genes were active, and which were inactive.” That’s because chromosomes are segregated into different neighborhoods for active and inactive genes—compartments still discernible after 52,000 years. Aiden’s team inferred the expression of genes linked to hair follicle development was altered in mammoth skin compared with elephant skin.
BOTTOM LINE
For mammoth buffs, the prospects for hearing that magnificent ice age beast bellow have grown a little brighter.
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