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In Drawers of Old Bones, New Clues to the Genomes of Lost Giants

DNA extracted from a 1,475-year-old jawbone reveals genetic blueprint for one of the largest lemurs ever.

By teasing trace amounts of DNA from this partially fossilized jawbone, nearly 1,500 years after the creature’s death, scientists have managed to reconstruct the first giant lemur genome. Credit: University of Antananarivo and George Perry, Penn State

If you’ve been to the Duke Lemur Center, perhaps you’ve seen these cute mouse- to cat-sized primates leaping through the trees. Now imagine a lemur as big as a gorilla, lumbering its way through the forest as it munches on leaves.

It may sound like a scene from a science fiction thriller, but from skeletal remains we know that at least 17 supersized lemurs once roamed the African island of Madagascar. All of them were two to 20 times heftier than the average lemur living today, some weighing up to 350 pounds.

Then, sometime after humans arrived on the island, these creatures started disappearing.

The reasons for their extinction remain a mystery, but by 500 years ago all of them had vanished.

Coaxing molecular clues to their lives from the bones and teeth they left behind has proved a struggle, because after all this time their DNA is so degraded.

But now, thanks to advances in our ability to read ancient DNA, a giant lemur that may have fallen into a cave or sinkhole near the island’s southern coast nearly 1,500 years ago has had much of its DNA pieced together again. Researchers believe it was a slow-moving 200-pound vegetarian with a pig-like snout, long arms, and powerful grasping feet for hanging upside down from branches.

A single jawbone, stored at Madagascar’s University of Antananarivo, was all the researchers had. But that contained enough traces of DNA for a team led by George Perry and Stephanie Marciniak at Penn State to reconstruct the nuclear genome for one of the largest giant lemurs, Megaladapis edwardsi, a koala lemur from Madagascar.

Ancient DNA can tell stories about species that have long since vanished, such as how they lived and what they were related to. But sequencing DNA from partially fossilized remains is no small feat, because DNA breaks down over time. And because the DNA is no longer intact, researchers have to take these fragments and figure out their correct order, like the pieces of a mystery jigsaw puzzle with no image on the box.

Bones like these are all that’s left of Madagascar’s giant lemurs, the largest of which weighed in at 350 pounds — 20 times heftier than lemurs living today. Credit: Matt Borths, Curator of the Division of Fossil Primates at the Duke Lemur Center

Hard-won history lessons

The first genetic study of M. edwardsi, published in 2005 by Duke’s Anne Yoder, was based on DNA stored not in the nucleus — which houses most of our genes — but in another cellular compartment called the mitochondria that has its own genetic material. Mitochondria are plentiful in animal cells, which makes it easier to find their DNA.

At the time, ancient DNA researchers considered themselves lucky to get just a few hundred letters of an extinct animal’s genetic code. In the latest study they managed to tease out and reconstruct some one million of them.

“I never even dreamed that the day would come that we could produce whole genomes,” said Yoder, who has been studying ancient DNA in extinct lemurs for over 20 years and is a co-author of the current paper.

For the latest study, the researchers tried to extract DNA from hundreds of giant lemur specimens, but only one yielded enough useful material to reconstitute the whole genome.

Once the creature’s genome was sequenced, the team was able to compare it to the genomes of 47 other living vertebrate species, including five modern lemurs, to identify its closest living relatives. Its genetic similarities with other herbivores suggest it was well adapted for grazing on leaves.

Despite their nickname, koala lemurs weren’t even remotely related to koalas. Their DNA confirms that they belonged to the same evolutionary lineage as lemurs living today.

To Yoder it’s another piece of evidence that the ancestors of today’s lemurs colonized Madagascar in a single wave.

Since the first ancient DNA studies were published, in the 1980s, scientists have unveiled complete nuclear genomes for other long-lost species, including the woolly mammoth, the passenger pigeon, and even extinct human relatives such as Neanderthals.

Most of these species lived in cooler, drier climates where ancient DNA is better preserved. But this study extends the possibilities of ancient DNA research for our distant primate relatives that lived in the tropics, where exposure to heat, sunlight and humidity can cause DNA to break down faster.

“Tropical conditions are death to DNA,” Yoder said. “It’s so exciting to get a deeper glimpse into what these animals were doing and have that validated and verified.”

See them for yourself

Assembled in drawers and cabinets cases in the Duke Lemur Center’s Division of Fossil Primates on Broad St. are the remains of at least eight species of giant lemurs that you can no longer find in the wild. If you live in Durham, you may drive by them every day and have no idea. It’s the world’s largest collection.

In one case are partially fossilized bits of jaws, skulls and leg bones from Madagascar’s extinct koala lemurs. Nearby are the remains of the monkey-like Archaeolemur edwardsi, which was once widespread across the island. There’s even a complete skeleton of a sloth lemur that would have weighed in at nearly 80 pounds, Palaeopropithecus kelyus, hanging upside down from a branch.

Most of these specimens were collected over 25 years between 1983 and 2008, when Duke Lemur Center teams went to Madagascar to collect fossils from caves and ancient swamps across the island.

“What is really exciting about getting better and better genetic data from the subfossils, is we may discover more genetically distinct species than only the fossil record can reveal,” said Duke paleontologist Matt Borths, who curates the collection. “That in turn may help us better understand how many species were lost in the recent past.”

They plan to return in 2022. “Hopefully there is more Megaladapis to discover,” Borths said.

A fossil site in Madagascar. Courtesy of Matt Borths, Duke Lemur Center Division of Fossil Primates

CITATION: “Evolutionary and Phylogenetic Insights From a Nuclear Genome Sequence of the Extinct, Giant, ‘Subfossil’ Koala Lemur Megaladapis Edwardsi,” Stephanie Marciniak, Mehreen R. Mughal, Laurie R. Godfrey, Richard J. Bankoff, Heritiana Randrianatoandro, Brooke E. Crowley, Christina M. Bergey, Kathleen M. Muldoon, Jeannot Randrianasy, Brigitte M. Raharivololona, Stephan C. Schuster, Ripan S. Malhi, Anne D. Yoder, Edward E. Louis Jr, Logan Kistler, and George H. Perry. PNAS, June 29, 2021. DOI: 10.1073/pnas.2022117118.

Do DNA Tests Sell Rosy Ideas About Race for Profit?

Earlier this year,  the online DNA testing company Ancestry.com faced a media firestorm and social media backlash after posting a controversial ad on its YouTube page.

The DNA testing company Ancestry.com took down its ad, “Inseparable,” in April 2019 in response to criticism that it romanticized slavery.

Titled “Inseparable,” the 30-second ad depicted a white man in the antebellum South asking an African-American woman to flee to the North with him. Before the woman can answer, the piece cuts to a tagline: “Only you can keep the story going. Uncover the lost chapters of your family history with Ancestry.” Many criticized the ad’s historical inaccuracy, showcasing a rosier portrayal of a complicated past. To extinguish flames, Ancestry completely pulled the ad from its platforms.

A recent Duke study of dozens of other ads across multiple DNA testing companies shows that this isn’t the only example of mixed messaging about race and identity from the world of genetic ancestry tests.

The tests are quite simple: order a kit, send off a saliva sample and receive an ethnicity estimate within weeks. A test taker’s ethnicity is broken down into percentages based off their DNA matches compared to a globally referenced DNA database. Kits can range in price from $79 to$400. Sales of DNA testing kits had reached 12 million people by 2017, as reported by ScienceLine.

As part of the six-week summer research program Story+, Duke students Dakota Douglas, Mona Tong and Madelyn Winchester analyzed the messaging in 90 video ads from the companies 23andMe, AncestryDNA and MyHeritageDNA to see what they promise consumers.

Many of the ads lured customers with promises of a newfound identity and possible family members, the team found. One Ancestry.com ad, entitled “Kyle,” depicts a customer whose childhood was steeped in German culture, but discovers as an adult that he is also part Scottish and Irish. He happily “traded in his lederhosen for a kilt,” completely forgoing his previous heritage and reducing a newly discovered culture to stereotypes.

“There were a lot of advertisements similar to that one,” said team member Mona Tong. “Many found a new identity embracing it fully despite a lack of any cultural connections.”

“Kyle” illustrates a phenomenon described in a 2018 study from the University of British Columbia, which found that people tended to “cherry-pick” the results, identifying more with certain ethnicities and cultures to appear different. Whites were more likely to see their results as “transformational” than their nonwhite counterparts.

“It’s not a bad idea to test your genes for medical reasons,” said Patricia Bass, the team’s project mentor. “However, these ads can be misleading by assuming that someone’s cultural and racial heritage are determined by genes.”

While the majority of subjects featured within the ads were white, the few ads that featured people of color often glossed over the complicated history of someone’s lineage or conveniently left out difficult topics. Ancestry’s “Anthem” ad detailed historical reenactments of an African tribal women, prohibition gangsters, a man fleeing England for America and Native Americans somberly heading to a new land. A voiceover speaks with inspiration ending with a shot of a biracial woman.

In marketing the idea that we are all one, the ads fetishized mixed-race subjects, while ignoring the genocide and displacement of people, the team found.

The team hopes future research will further examine the impact of these ads on people’s view of identity. Importantly, one could note if there were any focus groups to test these ads before release.

“It furthers the idea of colorblindness,” Tong said. “It assumes that relationships are contingent upon common ancestry and genes.”

“In a way, companies are trying to help by focusing on the interconnectivity and commonalities between people,” Tong said. “But it hurts more than it helps.”

Story+ is a six-week undergraduate research program offered through the John Hope Franklin Humanities Institute and Bass Connections, with support from the Duke University Libraries and Versatile Humanists at Duke.

By Deja Finch

Scents Are Key to Lemur Nightlife

LEMUR SUPERPOWER #457:  Some lemurs can safely digest cyanide in amounts sufficient to kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. To add to their list of superpowers, lemurs also have especially keen powers of scent.

Buried in the nose of Fuggles the mouse lemur are specialized pheromone receptors that help her distinguish friend from foe in the dark of night, when mouse lemurs are active.

By Robin Ann Smith

If you could pick one superpower, consider taking inspiration from lemurs. Some lemurs can safely digest cyanide in amounts that would kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. Still others have keen powers of scent, with the ability to find mates and avoid enemies in the darkness by smell alone.

Research by biologist and Duke Lemur Center director Anne Yoder suggests that the molecular machinery for sniffing out pheromones — much of which has gone defunct in humans and many other primates — is still alive and well in lemurs and lorises, our distant primate cousins.

Lemurs use scents to mark the boundaries of their territories, distinguish males from females and figure out whether another animal is friend or foe. When a lemur gets a whiff of another animal, specialized pheromone receptors in the lining of the nose transmit the information to the brain, triggering instinctive urges like mating, defense and avoiding predators.

The receptors are proteins encoded by a family of genes called V1Rs. First identified in rats in the mid-1990s, V1R genes are found in animals ranging from lampreys to humans. But the proportion of these pheromone-detection genes that actually functions varies greatly from one species to the next, Yoder said last week in a roundtable discussion hosted by Duke’s Science & Society program.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Studies suggest that as much as 90% to 100% of the pheromone-detection genes in humans consist of disabled pieces of DNA, called pseudogenes.

“Our pheromone-detection genes are so boring — we don’t have many of them, and almost all of them are broken,” Yoder said.

But in lemurs and lorises — whose ancestors split off from the rest of the primate family tree more than 60 million years ago — the proportion of pheromone-detection genes that is still intact is much higher.

In a study published this year, Yoder and colleagues analyzed the DNA of 19 species and subspecies of lemurs and lorises, looking for subtle differences in their V1R genes. They found that one group — the mouse lemurs — has the highest proportion of intact V1R sequences of any mammal yet studied.

To find out which genes are linked to which scents, Yoder and her colleagues plan to take DNA sequences from pheromone-detecting genes in lemurs, insert them into mice, and expose the mice to different scents to see how they respond.

An ability to sniff out the right mates — and avoid being seduced by the wrong suitors — may have served as a mating barrier that allowed lemur species to diverge after arriving in their island home of Madagascar, helping to explain how the more than 70 living species of lemurs came to be, Yoder says.

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