Million-year-old mammoth teeth produce the world’s oldest DNA

Scientists have sequenced the oldest DNA so far, breaking a symbolic barrier in studying ancient genomes and opening an unprecedented window into the evolution of the extinct Ice Age giants of North America: the Colombian and woolly mammoths.

The feat is unlikely to turn on a mammal Jurassic Park style recreation; The study is not the first to sequence the genome of a mammoth, nor does it bring humanity closer to resurrecting a mammoth. Instead, the study of DNA over a million years, published in Nature on Wednesday, it sets a milestone for the study of the rapid growth of ancient DNA, nearly doubling the record for the oldest genome ever sequenced.

The DNA comes from three mammoth molars found in Siberia in the early 1970s by Russian paleontologist Andrei Sher, a legend in the field for his mammoth research. Researchers estimate that the youngest of the three teeth is between 500,000 and 800,000 years old, while the two oldest are between 1 million and 1.2 million years old. The next oldest DNA ever sequenced came from a nearly 700,000-year-old horse fossil found in the Canadian Yukon Territory.

“Breaking this somewhat magical barrier of more than a million years opens a new window of time, so to speak, and an evolutionary perspective,” says study lead author Tom van der Valk, a bioinformatician at Uppsala University who worked in the study while at the Center for Paleogenetics in Stockholm, Sweden.

The findings add surprising detail to scientists’ picture of how the mammoths of North America evolved. For one thing, ancient tooth DNA strongly suggests that the North American Columbian mammoth, one of North America’s major mammoth species, is a hybrid that arose 400,000 to 500,000 years ago, a fact that is only revealed because the oldest DNA in the study dramatically precedes this cross. “If we look at higher-order organisms like vertebrates, I can’t think of a single example where people have sampled before the origin of a species,” says study co-author Love Dalén, a geneticist at the Center for Paleogenetics.

The further back in time DNA records can go, the more scientists can learn about how evolution works. The success of the study also implies that, under the perfect conditions, even deeper glimpses of the evolutionary past may be possible, possibly a few million years ago, say its authors. (If it is older than that, the DNA would break into pieces too small to reassemble.)

Work on the teeth began in 2017, when the Center for Paleogenetics received samples of the teeth from the Russian Academy of Sciences. Dressed in protective suits now terrifyingly familiar in the COVID-19 era, a team led by geneticist Patrícia Pečnerová, a postdoctoral researcher now at the University of Copenhagen in Denmark, ground 50 milligrams of bone powder from each sample. Then, Pečnerová carefully extracted small amounts of DNA from each pinch of powder with a series of chemical baths, which concentrated the DNA into tiny droplets of liquid no bigger than peppercorns.

“Basically, I’m in a cocoon, with a mask and a face shield, really trying to minimize contamination,” says Pečnerová. “A simple [human] the cell could fall into the tube ”and ruin the sample.

Sequencing this DNA was only the first step. Next, van der Valk and his colleagues had to make sure to focus only on DNA fragments that were authentically ancient and of authentically mammoth origin. After all, the teeth had been buried for more than a million years in microbe-laden permafrost, and had been unearthed and manipulated by countless scientists for nearly five decades. Despite the best efforts to prevent contamination, the researchers had to deal with any extra DNA that the teeth had collected on their travels.

After weeks of computationally processing the sequenced DNA, the team was able to precisely identify mammoth DNA fragments as short as 35 base pairs and map them into a genome that, in life, was more than three billion base pairs.

A surprise sequence

The new study already sheds light on how the mammoths of North America evolved. To the researchers’ surprise, the DNA sequences in the new study are so old that they predate the origins of the Columbian mammoth, one of the two main species of mammoth that ever roamed North America, giving scientists an insight. new perspective on how mammoths evolved.

1.5 million years ago, relatives of the steppe mammoth from Europe and Asia had come to North America from Siberia, crossing a land bridge now covered by the Bering Strait. These newcomers later gave rise to the Columbian mammoth. Around 100,000 to 200,000 years ago, North America was home to at least two main types of mammoths: woolly mammoths in the north and Columbian mammoths as far south as Mexico. Researchers also knew from past genetic studies that Colombian mammoths and woolly mammoths interbred.

Paleontologists have long used the distinctive upper molars of mammoths to help separate the different species. Based on fossil mammoth teeth, paleontologists had traditionally assumed that the mammoths present in North America after about 1.5 million years ago were Colombian mammoths. But while the fossil tooth record shows continuity, the genetic record in the new DNA study reveals changes.

Two of the mammoth genomes in the new study belong to the lineage that later gave rise to woolly mammoths. But the DNA from the oldest of the three teeth, nicknamed Krestovka by scientists after the river near which it was found, appears to belong to a previously unknown genetic lineage, one that about 1.5 million years ago split from the lineage it contains. the other two teeth. .

When van der Valk’s team compared the mysterious mammoth genome with previously sequenced Columbian mammoth DNA, the researchers came to a surprising conclusion: The Columbian mammoth is a hybrid that emerged 400,000 to 500,000 years ago, after it was crossed between Krestovka mammoths and Siberian woolly mammoths. somewhere in Siberia, North America or Beringia, the land bridge that once linked them together.

After a second interbreeding event that took place in North America roughly 200,000 years ago, the Columbian mammoth obtained another 11 to 13 percent of its genome from woolly mammoths. By the time the Columbian mammoth became extinct around 12,000 years ago, roughly three-fifths of its genome dated back to the woolly mammoth, while the other two-fifths dated back to the enigmatic Krestovka mammoth, which is only known from the DNA contained within. . a single tooth.

The study also shows how well and how early mammoths adapted to the cold. Ancient DNA studies had delved into the genetic details of how the woolly mammoth thrived at low temperatures. But many of the genetic variants behind the woolly mammoth’s ability to withstand cold first appeared in much older mammoths. The new study finds that more than 85 percent of these woolly variants were already in Siberian steppe mammoths, ancestral cousins ​​of woolly mammoths, more than a million years ago.

At that million-year mark, mammoths were already living at high latitudes, according to fossil evidence, so it’s not surprising that these icy titans adapted to withstand the cold. However, the study provides unique insight into the pace of this winterization process. Mammoths appear to have developed these cold-adapted genetic variants at a more or less constant rate, not in bursts.

Details in DNA

Paleontologists say the revelation that Colombian mammoths were hybrids will further fuel an ongoing reassessment of the North American mammoth fossil record.

Recent research comparing fossil mammoth teeth to genetic family trees has found that, far from being dead rings for different species of mammoths, the shape and shape of the teeth overlap considerably from region to region in North America. The new study underscores this point: There is not much change in North American fossil mammoth teeth before and after 500,000 years ago, even though the genetic changes that produced the Columbian mammoth were immense.

“Without genetics, we are usually looking at morphology or changes in shape, and without those changes in shape, we can’t document changes in species,” says Lindsey Yann, paleontologist at Waco Mammoth National Monument in Texas. . “When you add that genetic component, we can really separate things and we have the data to prove it.”

For study co-author Adrian Lister, a paleontologist at the Natural History Museum in London and one of the world’s leading mammoth experts, the study also highlights a lingering tension: how to define North American mammoth teeth in cases where they are still missing. DNA. If, genetically speaking, Columbian mammoths did not appear until 400,000 to 500,000 years ago, how should paleontologists define older mammoth teeth that would otherwise look identical? Until now, no one has published DNA from North American mammoth teeth more than half a million years old.

To further complete the puzzle, Dalén says, he and his colleagues want to try applying their record skills to mammoth teeth from North America. The team has already identified a 500,000-year-old mammoth tooth from Canada, as well as a 200,000-year-old tooth that likely belonged to a woolly mammoth, as potential candidates for future sequencing.

And now that scientists have crossed the million-year barrier, it’s only a matter of time before even older DNA reveals its secrets. “That’s the million dollar question,” says Dalén. “We’ve seen the data that we have, and I think it would be relatively easy to go beyond two million, if we had a good sample.

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