Scientists ‘Resurrect’ Mutated Genes of Wrangel Island Mammoths

Woolly mammoths (Mammuthus primigenius) were among the most abundant cold adapted species during the Pleistocene. Their once large populations went extinct in two waves, an end-Pleistocene extinction of continental populations followed by the mid-Holocene extinction of relict populations on St. Paul Island, a small island in the middle of the Bering Sea, 5,600 years ago, and on Wrangel Island, a remote Arctic refuge off the coast of Siberia, 4,000 years ago. To learn about the plight of these giant creatures and the forces that contributed to their extinction, a team of researchers has ‘resurrected’ Wrangel Island mammoths’ mutated genes. The goal was to study whether the genes functioned normally. They did not.

This is an artist’s rendition of a woolly mammoth. Image credit: Flying Puffin / CC BY-SA 2.0.

“The key innovation of our paper is that we actually resurrect Wrangel Island mammoth genes to test whether their mutations actually were damaging (most mutations don’t actually do anything),” said Dr. Vincent Lynch, an evolutionary biologist at the University at Buffalo.

“Beyond suggesting that the last mammoths were probably an unhealthy population, it’s a cautionary tale for living species threatened with extinction: if their populations stay small, they too may accumulate deleterious mutations that can contribute to their extinction.”

To conduct the study, Dr. Lynch and his colleagues first compared DNA of a Wrangel Island mammoth to that of three Asian elephants and two more ancient mammoths that lived when mammoth populations were much larger.

The scientists identified a number of genetic mutations unique to the Wrangel Island mammoth.

Then, they synthesized the altered genes, inserted that DNA into cells in Petri dishes, and tested whether proteins expressed by the genes interacted normally with other genes or molecules.

The researchers did this for genes that are thought or known to be involved in a range of important functions, including neurological development, male fertility, insulin signaling and sense of smell.

“In the case of detecting odors, for example, we know how the genes responsible for our ability to detect scents work,” Dr. Lynch said.

“So we can resurrect the mammoth version, make cells in culture produce the mammoth gene, and then test whether the protein functions normally in 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.”

This study builds on prior work by other scientists, such as a 2017 paper in which authors identified potentially detrimental genetic mutations in the Wrangel Island mammoth, estimated to be a part of a population containing only a few hundred members of the species.

“The results are very complementary,” Dr. Lynch said.

“The 2017 study predicts that Wrangel Island mammoths were accumulating damaging mutations.”

“We found something similar and tested those predictions by resurrecting mutated genes in the lab.”

“The take-home message is that the last mammoths may have been pretty sick and unable to smell flowers, so that’s just sad.”

The results were published in the journal Genome Biology and Evolution.

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Erin Fry et al. Functional architecture of deleterious genetic variants in the genome of a Wrangel Island mammoth. Genome Biology and Evolution, published online February 7, 2020; doi: 10.1093/gbe/evz279