From alpacas to yaks, mammalian DNA reveals its secrets

From alpacas to yaks, mammalian DNA reveals its secrets

To learn more about humans, a large international team of scientists has spent years tracking down some of the strangest creatures on Earth. They camped out on an Arctic ice floe to harvest narwhal DNA with a tusk, captured a tiny bumblebee bat in a cave-rich region of Southeast Asia, and ventured behind the scenes to a Caribbean zoo to sample the blood from the sunnondon from the thin muzzle. , one of the few venomous mammals in the world.

The researchers compared the genomes of these mammals with those of a wide assortment of others, including an aardvark, a meerkat, a star-nosed mole and a human. In doing so, they were able to identify stretches of DNA that have barely changed over eons of mammalian evolution and are therefore likely vital to human health and functioning.

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

What incredibly cool things can those 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 the Zoonomia Project. We always like to think that humans are the most special species. But it turns out they were really quite boring in a lot of ways.

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

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

Sequencing many genomes is not trivial, said Michael G. Campana, a computational genomics scientist at the Smithsonians National Zoo and Conservation Biology Institute, who was not part of the project. What’s really important is actually using this data.

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

To look for the basis of exceptional animal talents, scientists looked for genetic sequences that had evolved unusually rapidly in species that shared a certain trait, such as the ability to hibernate.

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

Many hibernating species also have exceptional longevity, Dr Karlsson said, leading her to ask: Do changes in that gene contribute to their long life?

Researchers have also explored the sense of smell of mammals. Animals have a large assortment of different olfactory receptors, each capable of binding to certain odor-causing molecules; species with more olfactory receptor genes generally have sharper senses of smell.

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

The agouti turns out to have one of the best olfactory repertoires of any mammal, for totally unknown reasons, Dr. Karlsson said. It’s a reminder of how much diversity is out there that we know nothing about. (Dogs, he noted, haven’t proven particularly special in this regard.)

On the other hand, cetaceans, a group that includes dolphins and whales, have a greatly reduced number of olfactory receptor genes, which makes sense given their aquatic habitats. They communicate in other ways, said Kerstin Lindblad-Toh, a geneticist at the Broad Institute and Uppsala University and the other leader of the Zoonomia Project.

Species with more olfactory receptor genes also tended to have more olfactory turbinates, bony structures in the nasal cavity that aid in smell. The findings suggest that while some traits are important, they evolve in multiple ways, said Dr. Lindblad-Toh.

He added, I think one of the important things with our dataset is that it generates 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 epidemic, a relay of sled dog teams delivered an emergency supply of antitoxin to Nome, Alaska, which had been cordoned off by snow. Balto, one of the dogs that ran the last 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 have now used a small piece of that taxidermied fabric to learn more about the famous sled dog and its canine contemporaries. We saw it as a small challenge, said Kathleen Morrill, author of the Balto paper, who carried out the research as a graduate student at UMass Chan Medical School and is now a senior scientist at Colossal Biosciences. Here’s this fellow, really 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 fewer potentially harmful mutations. This finding likely stems from the fact that sled dogs are typically bred for physical performance and can be a mix of breeds.

Balto also had an assortment of genetic variants that weren’t present in wolves and were rare or missing in modern purebred dogs, the researchers found. Many variants were in genes involved in tissue development and may have influenced a variety of traits important to sled dogs, such as skin thickness and joint formation. Balto had two copies of these variants, one inherited from each parent, meaning they were probably at least somewhat common in other Alaskan sled dogs at the time.

We have this much clearer picture of what its population was like and what it would look like, said Katie Moon, a postdoctoral researcher at the University of California, Santa Cruz, and author of the paper. And that photo is of really well adjusted working sled dogs.

Scientists have long debated how and when today’s diverse assortment of mammals came about. Did the mammalian family tree branch only after the extinction of the dinosaurs some 66 million years ago? Or did the process largely take place before the catastrophe?

A new analysis with Zoonomia genomes suggests the answer is both. Mammals began to diversify about 102 million years ago, when the Earth’s continents were breaking up and sea levels began to rise. This isolated the predecessors of modern lineages across 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 came after the extinction of the dinosaurs, the researchers found, when the emergence of new lands and the demise of the reigning reptiles provided mammals with 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 is probably the largest of its kind in terms of trying to put mammals on a time scale.

The Zoonomia package more generally is a monumental body of work, he added. It will truly set the standard for our understanding of mammalian evolution in the future.

Mammals generally inherit two copies of most genetic sequences, one from each parent. Determining how closely these sequences match can provide insight into the size of past animal populations; long stretches of matching DNA can be a sign of inbreeding, for example.

An individual animal’s genome reflects how closely related its parents, grandparents, were going back in time, said Aryn Wilder, conservation geneticist at the San Diego Zoo Wildlife Alliance.

Dr Wilder and her colleagues used Zoonomia genomes to estimate the population sizes of different species throughout history. Compared to species that were historically abundant, those with small past populations had potentially more harmful genetic mutations and were 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 endangerment the IUCN considered unknown due to a lack of data: the killer whale, the blind mole rat of the Upper Galilee mountains and the Javan mouse deer (which looks exactly as advertised). . The findings suggested that orca may be at higher risk.

The approach could provide a quick way to prioritize species for more resource-intensive and thorough risk assessments, said Beth Shapiro, a paleogeneticist at the University of California, Santa Cruz, and an author of the study. It could be a relatively easy way to do conservation triage, she said.

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