Scientists resurrect mammoth's broken genes

February 07, 2020

BUFFALO, N.Y. -- Some 4,ooo years ago, a tiny population of woolly mammoths died out on Wrangel Island, a remote Arctic refuge off the coast of Siberia.

They may have been the last of their kind anywhere on Earth.

To learn about the plight of these giant creatures and the forces that contributed to their extinction, scientists have resurrected a Wrangel Island mammoth's mutated genes. The goal of the project was to study whether the genes functioned normally. They did not.

The research builds on evidence suggesting that in their final days, the animals suffered from a medley of genetic defects that may have hindered their development, reproduction and their ability to smell.

The problems may have stemmed from rapid population decline, which can lead to interbreeding among distant relatives and low genetic diversity -- trends that may damage a species' ability to purge or limit harmful genetic mutations.

"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)," says lead author Vincent Lynch, PhD, 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."

The study was published on Feb. 7 in the journal Genome Biology and Evolution.

Lynch, an assistant professor of biological sciences in the UB College of Arts and Sciences, joined UB in 2019 and led the project while he was at the University of Chicago. The research was a collaboration between Lynch and scientists at the University of Chicago, Northwestern University, University of Virginia, University of Vienna and Penn State. The first authors were Erin Fry from the University of Chicago and Sun K. Kim from Northwestern University.

To conduct the study, Lynch's team first compared the 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 researchers 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 scientists 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," Lynch says. "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."

The research builds on prior work by other scientists, such as a 2017 paper in which a different research team 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," Lynch says. "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."
-end-


University at Buffalo

Related Genes Articles from Brightsurf:

Are male genes from Mars, female genes from Venus?
In a new paper in the PERSPECTIVES section of the journal Science, Melissa Wilson reviews current research into patterns of sex differences in gene expression across the genome, and highlights sampling biases in the human populations included in such studies.

New alcohol genes uncovered
Do you have what is known as problematic alcohol use?

How status sticks to genes
Life at the bottom of the social ladder may have long-term health effects that even upward mobility can't undo, according to new research in monkeys.

Symphony of genes
One of the most exciting discoveries in genome research was that the last common ancestor of all multicellular animals already possessed an extremely complex genome.

New genes out of nothing
One key question in evolutionary biology is how novel genes arise and develop.

Good genes
A team of scientists from NAU, Arizona State University, the University of Groningen in the Netherlands, the Center for Coastal Studies in Massachusetts and nine other institutions worldwide to study potential cancer suppression mechanisms in cetaceans, the mammalian group that includes whales, dolphins and porpoises.

How lifestyle affects our genes
In the past decade, knowledge of how lifestyle affects our genes, a research field called epigenetics, has grown exponentially.

Genes that regulate how much we dream
Sleep is known to allow animals to re-energize themselves and consolidate memories.

The genes are not to blame
Individualized dietary recommendations based on genetic information are currently a popular trend.

Timing is everything, to our genes
Salk scientists discover critical gene activity follows a biological clock, affecting diseases of the brain and body.

Read More: Genes News and Genes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.