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Million-year-old mammoth DNA rewrites animal’s evolutionary tree

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Enlarge / A mammoth tusk thaws out of the ground in Siberia.

Ancient DNA has revolutionized how we understand human evolution, revealing how populations moved and interacted and introducing us to relatives like the Denisovans, a “ghost lineage” that we wouldn’t realize existed if it weren’t for discovering their DNA. But humans aren’t the only ones who have left DNA behind in their bones, and the same analyses that worked for humans can work for any other group of species.

Today, the mammoths take their turn in the spotlight, helped by what appears to be the oldest DNA ever sequenced. DNA from three ancient molars, one likely to be over a million years old, has revealed that there is a ghost lineage of mammoths that interbred with distant relatives to produce the North American mammoth population.

Dating and the mammoth family tree

Mammoths share something with humans: like us, they started as an African population but spread across much of the planet. Having spread out much earlier, mammoth populations spent enough time separated from each other to form different species. After branching off from elephants, the mammoths first split into what are called southern and steppe species. Later still, adaptations to ice age climates produced the woolly mammoth and its close relative, the North American mammoth, called the Columbian mammoth. All of those species, however, are extinct, and the only living relatives are the elephants.

We have obtained DNA from two of these species, the woolly and Columbian mammoths. These revealed both a number of adaptations to cold climates, and a small degree of interbreeding, as woolly mammoths made their way into North America and contributed a small amount (about 10 percent) to the genome of the Columbia population.

The new work focused on mammoth teeth found in Siberia, where conditions have favored both the preservation of remains and the preservation of the DNA they contain. The teeth come from layers of material that appear to have been deposited at the start of the most recent glacial period, which is when the ancestors of the woolly mammoth population should have been present in the area.

We don’t have precise dates for any of the teeth, as they appear to be too old for carbon dating. Instead, dates have been inferred using a combination of the species present in the deposits and the known timing of flips in the orientation of Earth’s magnetic field. In addition, the shape of the teeth provide some hints about what species they group with and provide some further indication of when they were deposited. In all, one tooth is likely to be at least a half-million years old, another about a million years old, and a third somewhat older still.

Very old, almost genomes

Previously, the oldest DNA obtained from animal remains is roughly the age of the youngest of these samples. But the researchers were able to recover some elephant-like DNA from each of the molars, although it was badly fragmented, and many individual bases were damaged. Researchers were able to isolate the full mitochondrial genome for each of the three teeth, as each cell contains many copies of this genome in each of its mitochondria. Only fragments of the nuclear genome could be obtained, however—at most, about 10 percent of one genome, and at worst under two percent. (Although less than two percent is still tens of millions of individual bases.)

Using the differences between the mammoth and elephant DNA and assuming a constant rate of mutation, the research team was able to derive independent dates for when each of the animals that left a tooth must have lived. Based on the mitochondria genome, the dates were 1.6 million, 1.3 million, and 900,000 years ago. For the two that had enough nuclear genome to analyze, the dates were 1.3 million and 600,000 years ago. The DNA-based dates for these two lined up nicely with each other and the date of the material they were found in. The oldest sample might be older than the deposit it’s in, and thus it might have been moved after death.

While these dates are fairly uncertain, they pretty clearly place two of the samples as the oldest DNA ever obtained from animals. And it would mean that these mammoths were living in Siberia shortly after ice-age conditions prevailed, although before there was a clear woolly mammoth lineage. They’d also predate the known appearance of mammoths in North America.

For all these reasons, the genomes potentially have a lot to say about the history of mammoths.

A ghost lineage and adaptations

And they do. The two younger samples are clearly on the same lineage that eventually produced the woolly mammoth, although they obviously predate the more recent samples that have yielded more complete genomes. But the oldest, from a site called Krestovka, looks like it’s from a separate lineage entirely. While it’s related to the woolly mammoth branch, it clearly diverged from it, and the analysis suggests that the split occurred at least 1.8 million years ago.

Krestovka also doesn’t have any direct modern descendants, indicating that it may have died off as a distinct population. But a lot of its DNA carried on as part of the Columbia mammoth genome. Apparently, at some point after the Krestovka, the lineage it was on interbred with the ancestors of the woolly mammoths. The result was a nearly 50/50 mix of the genomes of the two branches, the descendants of which migrated into North America and formed the Columbia mammoth population. Only much later did it meet the descendants, now a distinct woolly mammoth population, when they crossed into North America.

These animals were also already nearly as well adapted to the cold as their descendants, the woolly mammoths. The researchers identified 5,600 cases where the proteins of the mammoth genome differed from those in elephants. The ancient mammoths had already picked up over 85 percent of these changes, including ones involved in hair growth, fat deposits, temperature sensing, and handling of day/night cycles.

In other words, these things probably looked a lot like woolly mammoths, even if they were from a population that was still part of a larger cluster of mammoth ancestors living in Siberia at the time.

Mammoths may provide a relatively rare case, as we have a lot of their remains, and they lived in a part of the world where conditions are excellent for preserving DNA. But they also likely had a long generation time, so they underwent population changes at a far more gradual pace than many other species.

Even though getting DNA this old is rare, we might not need ancient DNA to get valuable information on how the species around us came into existence. And based on us and the mammoths, digging into these histories may provide lots of surprises.

Nature, 2021. DOI: 10.1038/s41586-021-03224-9  (About DOIs).

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Highest-Resolution Images of DNA Reveal It’s Surprisingly Jiggly

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Gif: A. L. B. Payne et al., 2021/Nature Communications

Scientists have captured the highest-resolution images ever taken of DNA, revealing previously unseen twisting and squirming behaviors.

Deoxyribonucleic acid, otherwise known as DNA, can be surprisingly active when crammed and contorted inside a cell, according to new research published in Nature Communications. These hidden movements were revealed by computer simulations fed with the highest-resolution images ever taken of a single molecule of DNA. The new study is exposing previously unseen behaviors in the self-replicating molecule, and this research could eventually lead to the development of powerful new genetic therapies.

“Seeing is believing, but with something as small as DNA, seeing the helical structure of the entire DNA molecule was extremely challenging,” Alice Pyne, the first author of the paper and a materials scientist at the University of Sheffield, said in a statement from the university. “The videos we have developed enable us to observe DNA twisting in a level of detail that has never been seen before.”

Atomic force microscopy image of a DNA molecule.
Image: A. L. B. Payne et al., 2021/Nature Communications

Scientists have previously used microscopes to gaze upon DNA and its twisted ladder-like configuration, but these were limited to static views of the molecule. What scientists haven’t been able to see is how the intense coiling of DNA affects its double-helical structure. To accomplish this, Pyne and her colleagues combined high-resolution atomic force microscopy (AFM) with molecular dynamics computer simulations, which revealed the writhing.

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Long, highly organized strands of DNA are crammed tightly inside our cells. As the new study shows, this results in some surprisingly dynamic physical behaviors.

Atomic force microscopy image of a DNA minicircle.
Image: A. L. B. Payne et al., 2021/Nature Comm

Agnes Noy, a lecturer at the University of York and a co-author of the study, said the microscopy images and the computer simulations agreed so well that they boosted the resolution of their experiments, allowing the team to “track how each atom of the double helix of DNA dances.”

For the study, the researchers analyzed DNA minicircles, in which a small strand is joined at both ends, forming a loop structure. DNA minicircles have been described before, and they’re believed to be important indicators of health.

Microscopic images of DNA minicircles in their “relaxed” position (i.e. no twists) revealed very little movement, but extra twists brought the loop to life, resulting in more vigorous movements. These dynamic moves may serve an important purpose, helping the DNA to find binding partners and facilitate growth.

The new atomic force microscopy shows, “with remarkable detail,” how “wrinkled, bubbled, kinked, denatured, and strangely shaped” the DNA minicircles really are, “which we hope to be able to control someday,” Baylor College of Medicine biologist Lynn Zechiedrich, who supplied the minicircles for the study, said in the University of Sheffield statement.

Indeed, further insights into DNA, and how it’s able to get so compact, could lead to the development of completely new medical interventions, including improved DNA-based diagnostics and therapeutics, according to the researchers.

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Early humans in China: DNA analysis points to later arrival than previously thought

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It suggested that Homo sapiens were in China at least 20,000 years earlier than early modern humans had been previously believed to have left Africa and spread around the world. It also tantalizingly hinted at the possibility that a different group of early humans could have evolved separately in Asia.

Not so fast, says the science in 2021. New research published Monday has suggested perhaps we shouldn’t be so eager to rewrite the time line on human origins.

DNA analysis of two human teeth found in the same cave, called Fuyan, plus teeth and other fossilized remains from four other caves in the same region, suggested that it was unlikely early modern humans were in China so early.

“Our new research means it is very unlikely that Homo sapiens reached China before 50,000 years ago. It is always possible that our species reached the region more than 100,000 years ago, but we would have to say that there is no convincing evidence in favor of this at present,” said Darren Curnoe, an associate professor at the Australian Museum Research Institute in Sydney and coauthor of the paper that published in the journal PNAS on Monday.

The researchers were able to extract DNA from 10 human teeth and establish the age of other materials in the caves, such as charcoal and animal teeth, using a range of different methods. The team found that the teeth were at least 16,000 years old, while the other materials were less than 40,000 years old.

“The 2015 study relied heavily on the results of a single dating method which determined the age of cave materials (flowstone) lying above and below the sediments containing the human teeth,” he said via email. Flowstone is a sheetlike deposit of rock formed by flowing water.

“It is well understood that the most reliable dates come directly from the materials of interest to archaeologists, in this case, the human teeth. Our new (dates), including direct ages, are far younger than previously suggested.”

The 2015 study measured the radioactive decay of uranium within cave deposits, not DNA.

Chris Stringer, research leader for human evolution at the Natural History Museum in London, said that the dates of Chinese fossilized teeth had always stood out and it was right to investigate them further using different methods.

However, he said the study, while interesting, didn’t definitively rule out early modern humans in China before 50,000 years ago.

Complex family tree

Untangling human ancestry is a complicated business, and recent research has indicated the human family tree is much more bushy and less linear than the traditional “Out of Africa” narrative, which suggested modern humans originated in Africa and made their first successful migration to the rest of the world in a single wave between 50,000 and 70,000 years ago.

Many different ancient hominins existed and coexisted before Homo sapiens emerged as the lone survivor, and there was interbreeding between different groups of early humans.

Some of these groups — like Neanderthals — are easily identified through the fossil record and archaeological remains, but others — like the Denisovans — have been largely identified by their genetic legacy.

Maria Martinón-Torres, director of the National Research Center on Human Evolution in Spain and an author of the 2015 study, said she welcomed the new data on the early presence of modern humans in China.

However, she noted that the two teeth from Fuyan Cave were uncovered in 2019 and didn’t belong to the original sample her team studied and published in 2015.

“The precise data about the location and morphology of the sample is crucial, but it is not provided in the paper,” she said.

“I agree that we should be working in improving the dates of all sites of interest, especially with direct dating when possible. However, at the moment, there is an increasing number of samples that would support the presence of H. sapiens outside Africa before 50 ka (50,000 years ago),” she said via email.

She noted that there are other discoveries in Saudi Arabia, Israel, Sumatra and Laos, and another site in China where a jawbone has been found, that support the presence of Homo sapiens outside Africa before 50,000 years ago.

One of the main factors supporting the idea that early modern humans left Africa around 50,000 years ago is that there is a strong signal in the genes of present-day human populations.

“We would say that Out of Africa after 70,000 years ago seems to be the dominant picture. We can’t preclude earlier dispersals in other regions, but certainly southern China seems to have been settled in this Out of Africa wave after 50,000 years ago,” Curnoe said via email.

However, Martinón-Torres said this doesn’t rule out the possibility that earlier groups of Homo sapiens wandered around Asia earlier — just as groups of other early humans like Neanderthals and Denisovans did.

“We had no expectations about the dating of these fossils and sites and would have been pleased if we had confirmed an early dispersal. It would certainly have made the history of our species much older than generally believed, and perhaps more interesting,” Curnoe said.

“Sadly, this seems not to be the case, at the least for southern China, according to our work.”

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Oldest DNA from poop contains a Neanderthal’s microbiome

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Enlarge / El Salt is an open-air rock shelter nestled against the base of a limestone cliff. Archaeological evidence tells us that Neanderthals lived here from around 60,700 to 45,200 years ago.

Candela et al. 2021

Biologist Marco Candela and his colleagues recently sequenced ancient microbial DNA from 50,000-year-old Neanderthal feces found at the El Salt archaeological site in Spain. The sequences included DNA from several of the microbes that still call our intestines home, as well as a few that have nearly vanished from today’s urban dwellers. According to Candela and his colleagues, their results suggest that the microscopic population of our guts may have been with us since at least 500,000 years ago, in the era of our species’ last common ancestor with Neanderthals.

Digging up Neanderthal poop

Mixed in with the layer of sediment that once formed the floor of a Neanderthal rock shelter in eastern Spain, archaeologists found millimeter-sized coprolites (fossil poop) and chemical signatures of human feces. An earlier study, published in 2014, sifted through the tiny coprolites to look for traces of Neanderthal diets. “These samples therefore represent, to our knowledge, the oldest known positive identification of human fecal matter,” wrote Candela and his colleagues.

They recently returned to El Salt for new samples, which they scoured for fragments of ancient DNA from the bacteria and other microbes that once lived in the intestines of Neanderthals. To weed out possible contamination, Candela and his colleagues sorted out the old, obviously degraded ancient DNA from the more pristine modern sequences. Most of the ancient DNA in the sediments came from bacteria that lived in the soil and water—tiny relics of the Pleistocene environment. But the rest included some familiar companions.

“There are probably more differences between the gut microbiomes from modern traditional (rural, hunter gatherers) populations and the modern industrial urban populations than between Neanderthal and modern traditional populations,” Candela, a biologist at the University of Bologna, told Ars.

What lived in a Neanderthal’s colon?

Humans and our closest living relatives, chimpanzees, share microbes from the same 24 phylogenetic families. To distinguish the gut microbiome of a human from that of a chimpanzee, you have to look at the genera, species, and sometimes even strains of the micro-organisms from each family. Each species of ape has a distinctive ecosystem of microbes, adapted to live with its immune system and the particular environment of its digestive tract that result from diet.

But some of the key players in modern gut microbiomes—the same genera and species swimming around in your intestines right now, modulating your immune system and breaking down your fiber intake—also lived inside Neanderthals.

In the 50,000-year-old feces-laden sediments from El Salt, Candela and his colleagues identified several key members of the human gut microbiome, like the aptly named Faecalibacterium and the somewhat ironically named Roseburia, both of which help break down dietary fiber into shorter chemicals that your body can metabolize. The team also found the genus Bifidobacterium, which helps digest sugars in milk and also plays a key role in the early childhood immune system. It’s “one of the human commensal bacteria of greatest current interest, due to its very promising potential as a biomarker of a healthy gut microbiome,” they wrote.

According to Candela and his colleagues, the findings suggest that some of the most important members of our gastrointestinal menagerie—the “keystone taxa,” as Candela and his colleagues put it—have been with us even longer than modern humans have existed. If our species and Neanderthals share a common core cast of gut microbes, it suggests that those keystone taxa probably lived in the guts of the last common ancestor both species shared.

Meet some really old friends

Some of those microbes, like the bacterial genus Bifidobacterium, seem to get passed down from mother to child. Others are acquired from the environment or from close contact with others. Those things don’t happen as much in modern urban settings (and that was true before the COVID-19 pandemic). Scientists who study the human microbiome have noticed that, for several generations, certain microbes have been disappearing from the intestines of urban populations in places like the US and Europe. That is mostly thanks to the use of certain medications and disinfectants; a sparkling clean house is, it turns out, a double-edged sword.

The disappearing bacteria include genera in the family Spirochaetaceae, along with the genera Prevotella and Sesulfovibrio. Microbiome researchers call them “old friends,” and their presence in the long-buried Neanderthal feces at El Salt suggests that these microbes are very old friends indeed.

And that’s what Candela meant when he told Ars that modern hunter-gatherers’ gut microbiomes have more in common with Neanderthals than with modern people in industrialized cities. Our gut microbes have changed more in the last few centuries or decades of industrialization and urbanization than they did since our species diverged from Neanderthals.

“The most dramatic gut microbiome change in our evolutionary history is occurring now in modern industrial societies,” Candela told Ars.

Two species, both alike in gut bacteria

Besides underscoring how much biodiversity we’re losing in our own guts, the Neanderthal gut microbiome holds some clues about how our extinct cousins lived.

For instance, the presence of those fiber-fermenting genera like Roseburia, Ruminococcus, and Faecalibacterium told Candela and his colleagues that plants had played an important role in the diet of Neanderthals and our last common ancestors—and probably even earlier members of our genus. That’s a line of evidence that can help supplement what paleoanthropologists know based on the teeth of other hominins, as well as traces of food found at some Neanderthal sites.

And Candela and his colleagues also noticed DNA from genera like Bacteroides, Bifidobacterium, and the brilliantly named Coprococcus, all of which help turn cholesterol into compounds like coprostanol, the fecal biomarker that identified the fecal sediments in the first place. Their presence suggests that Neanderthals needed a bit of help to metabolize cholesterol from foods like animal fats, meat, and eggs. That’s not terribly different from ancient or modern human diets (though modern industrialized populations arguably take the cholesterol thing to a whole new level).

In the end, the world’s only known Neanderthal poop tells us something interesting but not terribly surprising: Neanderthals were a lot like us. “We were expecting this overall, as the two lineages are very close from the evolutionary point of view,” Candela told Ars.

Communications Biology, 2021 DOI:  10.1038/s42003-021-01689-y  (About DOIs).

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