From alpacas to yaks, mammalian DNA offers its secrets

From alpacas to yaks, mammalian DNA offers its secrets

To learn more about humans, a large international team of scientists spent years searching for some of the strangest animals on Earth. They camped on an Arctic ice floe to collect DNA from a tusked narwhal, netted a tiny bumblebee bat in a cave-rich region of Southeast Asia, and ventured behind the scenes at a Caribbean zoo to draw blood from a slender-snouted solenodon. , one of the few venomous mammals in the world.

The researchers compared the genomes of these mammals to a variety of other species, including aurvarks, meerkats, star-nosed moles, and humans. In doing so, they were able to identify stretches of DNA that have barely changed over the evolutionary ages of mammals and are therefore critical to human health and functioning.

The genetic database they assembled includes the complete genomes of 240 species, covering more than 80 percent of the planet’s mammals (and including humans). It can help scientists answer a variety of questions about other animals, such as when and how they evolved and the biological basis for some of their unusual talents.

“What amazingly cool things can those species do that humans can’t?” said Elinor Carlson, a geneticist at the UMass Chan Medical School and Broad Institute and co-leader of what is known as the Zoonomia Project. “We always like to think of humans as the most special species. But it turns out we’re actually boring in a lot of ways.

The Zoonomia data set has limitations. It contains only one genome per species (with the exception of the domestic dog, which was sequenced twice), and thousands of mammals are missing.

But in a new package of papers published in Science on Thursday, the Zoonomia team demonstrated the power of this kind of multi-species data. And that’s just the beginning.

Computational genomics scientist Michael G. of the Smithsonian’s National Zoo and Conservation Biology Institute. “Sequencing a lot of genomes is not trivial,” Campana said. This was not part of the project. “What’s really important is to actually use this data.”

Here are some things Zoonomia scientists are already doing with it:

To explore the basis of extraordinary animal talent, scientists looked for genetic sequences that evolved unusually quickly in species that shared certain traits, such as the ability to hibernate.

In one analysis, the researchers focused on deep hibernators, such as the fat-tailed dwarf lemur and the large mouse-eared bat, which can maintain low body temperatures for days or weeks at a time. The researchers found evidence of “accelerated evolution” in several genes, including one that is known to help protect cells from temperature-related stress and another that inhibits cellular pathways related to aging.

“Many dormant species also have extraordinary longevity,” Dr. Carlson said, she wonders: Do changes in that gene contribute to their longevity?

Researchers also explored mammals’ sense of smell. Animals have a wide range of different olfactory receptors, each capable of binding specific odorant molecules; Species with more olfactory receptor genes usually have a stronger sense of smell.

When the Zoonomia team counted the number of these genes in each species, the African savannah elephant took the top spot with 4,199. The nine-banded armadillo and Hoffman’s two-toed sloth followed, while the Central American agouti came in fourth.

The agouti “turns out to have the best olfactory repertoire of any mammal, for reasons completely unknown,” Dr. Carlson said. “It’s a reminder of how much diversity there is that we don’t know anything about.” (Dogs, she noted, have not proven to be “particularly special” in this regard.)

On the other hand, cetaceans—a group that includes dolphins and whales—have significantly fewer olfactory receptor genes, which makes sense given their watery habitats. “They communicate in other ways,” said Kerstin Lindblad-Toh, a geneticist at the Broad Institute and Uppsala University and another leader of the Zoonomia project.

Species with more olfactory receptor genes also have more olfactory turbinates, bony structures in the nasal cavity that aid in olfaction. The results suggest that “if certain traits are important, they evolve in many ways,” Dr. Lindblad-Toh said.

She added, “I think one of the important things with our data set is that it creates genome sequencing for so many different species that people can start looking at their favorite characteristics.”

In February 1925, in the midst of a diphtheria outbreak, a relay of sled dog teams delivered an emergency supply of antitoxin to Nome, Alaska, which had been isolated by ice. Balto, a dog who ran the final leg of the relay, became famous; When he died several years later, his taxidermied body was put on display at the Cleveland Museum of Natural History.

A team of Zoonomia researchers has now used a small piece of that taxidermied tissue to learn more about the celebrity sled dog and its canine contemporaries. “We saw this as a small challenge,” said Kathleen Morrill, author of the Balto paper, who did the research as a graduate student at UMass Chan Medical School and is now a senior scientist at Colossal Biosciences. “Here’s this guy, who’s really famous. We don’t know much about its biology. What can we say about its genome?

Balto, they found, was genetically “healthier” than modern purebred dogs, with more heritable genetic variation and fewer potentially harmful mutations. That finding stems from the fact that sled dogs are usually bred for physical performance and can be a mix of breeds.

The researchers found that Balto also had a range of genetic variations that were not present in wolves and are rare or missing in modern purebred dogs. Many of the variants were in genes involved in tissue development and could affect various traits important to sled dogs, such as skin thickness and joint structure. Balto had two copies of these variants, one inherited from each parent, which means they were probably at least somewhat common among other Alaskan sled dogs at the time.

“We get such a clear picture of what it was like and what its population might have looked like,” said Katie Moon, a postdoctoral researcher at the University of California, Santa Cruz and an author of the paper. “And that picture is of a really well-suited working sled dog.”

Scientists have long debated how and when today’s diverse range of mammals came into being. Did the mammal family tree branch out only after the extinction of the dinosaurs about 66 million years ago? Or was the process mostly done before the disaster?

A new analysis with Zoonomia genomes suggests the answer is both. Mammals were the first to diversify About 102 million years ago, when Earth’s continents were breaking apart and sea levels began to rise. “This separated the precursors of modern lineages on different land masses,” said William Murphy, an evolutionary geneticist at Texas A&M University and an author of the paper.

But another burst of diversification followed the extinction of the dinosaurs, the researchers found, when the emergence of new land and the disappearance of the ruling reptiles gave mammals new habitats, resources and opportunities.

“It’s a really landmark paper,” said Scott Edwards, an evolutionary biologist at Harvard who was not involved in the research. “It’s probably the largest of its kind in terms of trying to put mammals on a time scale.”

The Zoonomia package more broadly is “a monumental body of work,” he added. “It will really set the standard for our understanding of mammalian evolution going forward.”

Mammals usually inherit two copies of most genetic sequences, one from each parent. Determining how closely these sequences match can provide insight into past animal population sizes; For example, a long stretch of matching DNA may be a sign of inbreeding.

An animal’s genome reflects “how closely related its parents were, grandparents, going all the way back,” said Aryan Wilder, a conservation geneticist at the San Diego Zoo Wildlife Alliance.

Dr. Wilder and his colleagues used Zoonomia genomes to estimate the population sizes of various species throughout history. Compared to historically abundant species, those with smaller past populations had more potentially harmful genetic mutations and were more likely to be listed as endangered by the International Union for Conservation of Nature.

The researchers also analyzed the genomes of three species whose extinction risk is considered unknown by the IUCN due to a lack of information: the killer whale, the blind mole rat of the Upper Galilee Mountains, and the Java mouse-deer (which looks exactly as advertised). The results suggest that killer whales may be most at risk.

The approach could provide a faster way to prioritize species for more thorough, resource-intensive risk assessments, said Beth Shapiro, a paleogeneticist at the University of California, Santa Cruz and study author. “It can be a relatively straightforward way to triage defenses,” she said.

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