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Inbreeding among the last woolly mammoths may have led to extinction

Some of the last mammoths on Earth suffered from mutated genes that reduced fertility, caused diabetes, affected their development and even kept them from being able to smell flowers, according to a new study.

While woolly mammoths were once plentiful across the northern hemisphere, they actually went extinct in two separate events. The first wave of mammoth extinction occurred on the heels of the last ice age and global warming led to the loss of their habitat, around 10,500 years ago.

But isolated populations of mammoths survived for much longer on St. Paul Island in Alaska and Wrangel Island, until about 5,600 years ago and 4,000 years ago, respectively. Wrangel Island is in the Arctic Ocean, located off the Siberian coast.

Previous research in 2017 identified genomic defects that likely had a detrimental effect on the Wrangel Island mammoths.

“When we did our own research on the Wrangel Island mammoth it was clear that it had a lot of bad mutations,” said Rebekah Rogers, author of the 2017 study and assistant professor at the University of North Carolina, Charlotte. ” We saw many genes that were broken and far more mutations than you would expect based on chance alone. How bad were the effects of these mutations? How did they change what was happening in cells or the ways that the animals could act?”

A new study, published recently in the journal Genome Biology and Evolution, took a closer look at those mutations. Rogers was not involved in the study.

Woolly mammoth genomes have been sequenced previously, so the researchers involved in the new study used a Wrangel Island mammoth genome and studied the genes and their mutations. These were compared with DNA from Asian elephants and mammoth DNA from animals that lived many years before the Wrangel Island mammoth, when their populations were plentiful.

The researchers found that the Wrangel Island mammoth’s genes were essentially broken. Sometimes mutations don’t necessarily have an affect. But in this case, the mutated genes had a detrimental effect on what is thought to be the last living mammoth population.

“The 2017 study predicts that Wrangel Island mammoths were accumulating damaging mutations,” said Vincent Lynch, lead study author and evolutionary biologist at the University at Buffalo. “We found something similar and tested those predictions by resurrecting mutated genes in the lab.”

The cause of extinction for these island mammoths is unknown, but researchers do know they suffered a rapid population decline due to their isolation. The small population would have led to inbreeding and reduced genetic diversity, according to the study.

They found that the mutations would have affected a variety of areas for the mammoths in their last days.

“Many of the mutated genes are involved in male fertility [making sperm, in particular], cognition and motor control, and the perception of smell, so we can be reasonable sure at least some of these things were not normal in the last mammoths,” Lynch said.

The researchers identified the altered genes of the Wrangel Island mammoth and inserted them into living cells to test how the mutations interacted.

“We know how the genes responsible for our ability to detect scents work,” Lynch said. To resurrect the mammoth gene, the researchers grew cells in a lab and tested whether the smell gene functions normally in those cells. “If it doesn’t — and it didn’t — we can infer that it probably means that Wrangel Island mammoths were unable to smell the flowers that they ate.”

The reduction in smell would make it more difficult for them to locate their food source. And the researchers also found evidence that they suffered from insulin signaling, causing diabetes.

“We’ve know for a while that as populations get smaller they tend to have an increased number of genetic mutations that contribute to disease,” Lynch said. “It’s one of the reasons animal breeders try to avoid inbreeding. No one wants to end up rulers of an empire but crippled like the Habsburgs!” (The Habsburg dynasty was a German royal family that ruled the Holy Roman Empire from 1438 until 1740, when the male line died out due to inbreeding. The inbreeding also led to facial deformities such as a large lower jaw and chin called the “Habsburg jaw,” and humped “Habsburg nose.”)

This new research aligns with previous studies about the decline of the Wrangel Island mammoths, such as Rogers’ 2017 study.

“Lynch’s group was able to take a more precise look at the biochemical changes,” Rogers said. “This was an interesting study because it showed how these mutations damaged smell or how they were likely to affect fertility. In the future, I expect researchers will be able to do more exciting studies like this to show how mutations in animals that are now long gone could have affected their biology.”

Lynch’s research has inspired more questions. The researchers want to know if the genetic changes were unique to the DNA of the one Wrangel Island mammoth genome they studied, or if they applied to the entire population. They’re also curious about other potential mutations and when they occurred on the timeline of the mammoth’s extinction. And only more data will tell the tale.

“The take-home message is that the last mammoths may have been pretty sick and unable to smell flowers, so that’s just sad,” Lynch said. “Beyond suggesting that the last mammoths were probably an unhealthy population, it’s a cautionary tale fora living species threatened with extinction: If their populations stay small, they too may accumulate deleterious mutations that can contribute to their extinction.”

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