What Can You Do With a Menagerie of Mammal Genomes?

To learn more about humans, a large international team of scientists spent years tracking down some of the strangest creatures on Earth. He camped on Arctic ice to collect DNA from one-tusked narwhals, captured tiny bumblebee bats in cave-rich regions of Southeast Asia and ventured behind the scenes at Caribbean zoos to draw blood from slender-snouted solenondons. , one of the few venomous mammals in the world.

The researchers compared the genomes of these mammals to various other species, including aardvarks, meerkats, star-nosed moles and humans. In doing so, they were able to identify stretches of DNA that have remained virtually unchanged over the years of mammalian evolution and may be essential to human health and function.

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

“What can an extraordinary species do that humans can’t?” said Elinor Karlsson, a geneticist at UMass Chan Medical School and the Broad Institute and co-leader of what is known as Project Zoonomia. “We always like to think of humans as the most special species. But it turns out that we are boring in many ways.

The Zoonomia data set has limitations. It contained only one genome per species (except domestic dogs, which were sequenced twice), and thousands of mammals were missing.

But in a new package of papers, published in Science on Thursday, the Zoonomia team shows the power of this multispecies data. And that’s just the beginning.

“Sequencing a large number of genomes is not trivial,” said Michael G. Campana, a computational genomics scientist at the Smithsonian’s National Zoo and Conservation Biology Institute, who was not part of the project. “The really important thing is to use the data.”

Here are some of the things Zoonomia scientists have done:

Open the base of special skills

In order to find the basis of the extraordinary talents of animals, scientists are looking for genetic sequences that rapidly evolve unusually in species that have certain traits, such as the ability to hibernate.

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

“Many hibernating species also have extraordinary longevity,” said Dr. Karlsson, led him to think: Do changes in these genes contribute to longevity?

The researchers also studied mammals’ sense of smell. Animals have a variety of different olfactory receptors, each capable of binding to molecules that cause bad odors; species with olfactory receptor genes are more likely to have a keen sense of smell.

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

agouti “has one of the best olfactory repertoires of any mammal, for reasons completely unknown,” Dr. Karlsson said. “It’s a reminder of the diversity that’s out there that we don’t know about.” (Dogs, he notes, don’t prove to be “specially special” in this regard.)

On the other hand, cetaceans – a group that includes dolphins and whales – have very few olfactory receptor genes, which makes sense given their watery habitat. “They communicate in other ways,” says 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 tend to have more olfactory turbinals, bony structures in the nasal cavity that aid in olfaction. The results show that “if certain traits are important, they will evolve in many ways,” said Dr. Lindblad-Toh.

He added, “I think one of the important things with data sets is to generate genome sequences for different species so that people can see the characteristics of interest.”

In February 1925, in the midst of a diphtheria outbreak, a relay of sled dog teams sent an emergency supply of antitoxin to Nome, Alaska, which had been isolated by snow. Balto, one of the dogs who ran the final leg of the relay, became famous; when he died a few years later, his taxidermied body was exhibited at the Cleveland Museum of Natural History.

A team of Zoonomia researchers has now used small pieces of that taxidermied tissue to learn more about celebrity sled dogs and their canine companions. “We see this as a small challenge,” said Kathleen Morrill, author of the Balto paper, who conducted the research as a graduate student at UMass Chan Medical School and is now a senior scientist at Colossal Biosciences. “Here’s this one guy, he’s very famous. We don’t know much about his biology. What can we say about his genome?”

Balto, they found, was genetically “healthier” than modern purebred dogs, with more inherited genetic variation and potentially dangerous mutations. These findings likely stem from the fact that sled dogs are typically bred for physical performance and may be a mix of breeds.

Balto also has several genetic variants that are absent in wolves and are rare or lost in modern purebred dogs, the researchers found. Many variants exist in genes involved in tissue development and may affect various traits important to sled dogs, such as skin thickness and joint formation. Balto has two copies of this Variant, one inherited from each parent, which means they were probably at least more common in other Alaskan sled dogs at the time.

“We’re getting a much clearer picture of where they are and how their population is,” said Katie Moon, a postdoctoral researcher at the University of California, Santa Cruz, and an author of the paper. “And the image is of a sled dog that can be adapted very well.”

Illuminating the timeline of evolution

Scientists have long debated exactly how and when the various mammals of today came into existence. Did the mammal family tree emerge only after the extinction of the dinosaurs, about 66 million years ago? Or does the process generally take place before the disaster?

A recent analysis of the Zoonomia genome suggests that the answer is both. The first mammals began to diversify about 102 million years ago, when the Earth’s continents broke apart and sea levels began to rise. “It isolated the predecessors of modern lineages on different continents,” said William Murphy, an evolutionary geneticist at Texas A&M University and an author of the paper.

But another explosion of diversification came after the extinction of the dinosaurs, the researchers found, when the emergence of new lands and the disappearance of reptiles gave mammals new habitats, resources and opportunities.

“This is a very important paper,” said Scott Edwards, an evolutionary biologist at Harvard, who was not involved in the research. “Probably the biggest of its kind in terms of trying to provide mammals on a time scale.”

The Zoonomia package more generally is “a monumental set of works,” he said. “This will set the standard for our understanding of mammalian evolution going forward.”

Predicting extinction risk

Mammals generally inherit at most two copies of their genetic sequence, one from each parent. Determining how close the sequences are can provide insight into past animal population sizes; The length of the corresponding DNA can be a sign of inbreeding, for example.

An animal’s genome reflects “how closely related it is to its parents, grandparents, all the way back,” says Aryn Wilder, a conservation geneticist at the San Diego Zoo Wildlife Alliance.

Dr. Wilder and his colleagues used the Zoonomia genome to estimate the population size of different species throughout history. Compared to historically abundant species, those with previously small populations have more dangerous genetic mutations and are more likely to be classified as threatened 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 lack of data: the killer whale, the blind mole rat of the Upper Galilee Mountains and the Javan deer (which looks exactly as advertised). These results suggest that killer whales may be at the highest risk.

The approach could provide a quick way to prioritize species for a more comprehensive and resource-intensive risk assessment, said Beth Shapiro, a paleogeneticist at the University of California, Santa Cruz, and an author of the study. “It can be an easy way to do conservation triage,” he said.