Welcome to the world of mammals: Scientists sequence DNA from 240 species around the world

Even before the mass extinction ended with the dinosaurs about 65 million years ago, mammals had already gained a humble but solid foothold.

It’s just one of the findings from scrutinizing the DNA of 240 different mammal species, a major effort to understand how hairy, milk-producing mammals, including humans, evolved to achieve such an amazing range of sizes, shapes and special abilities.

Scientists know about 6,500 species of living mammals that inhabit almost every environment on Earth, from cold oceans to high deserts. This international project, called Zoonomia, was designed to collect genetic material from the entire mammalian family tree.

The researchers obtained DNA from all kinds of mammalian creatures, such as caribou, armadillos, bats and bison. Their genetic menagerie eventually included 52 endangered species, such as the giant otter and the Amazon river dolphin, as well as primates such as chimpanzees and humans.

“We’re still only looking at a small fraction of mammals, but this is the biggest project we’ve ever done like this,” says Elinor Karlsson, director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard. that 80 percent of the mammalian families are represented in their collection.

After determining the sequence of chemical “letters” that made up the genetic code of each species, the researchers then “matched” those sequences so they could be comprehensively compared. This allowed them to see which genetic regions have remained constant over millions of years of evolution, suggesting that they contain essential biological instructions for building mammals.

They were also able to eliminate genetic differences between mammal species, which allowed them to examine the possible genetic basis of unique traits, such as the ability to hibernate or an extremely sensitive sense of smell.

“It turns out there’s a weird little South American rodent that nobody knows much about that has a huge number of olfactory genes and receptors,” Carlson says. “It kind of points to what we can discover when we just look at everything.”

She and her colleagues have now published 11 research reports in the journal Science which outlines some of their first efforts to understand what exactly makes a mammal at the genetic level.

And intriguingly, they found some clues about how one mammal Homo sapiensevolved to such a unique brain—a brain that can think like a mammal and develop complex computational programs to compare and contrast the vast amounts of data throughout that genetic code.

When mammals began to appear

Scientists have long debated when mammals first appeared on Earth and how and why they began to diversify, eventually inhabiting almost every possible habitat and ranging in size from tiny bats to giant whales.

“The reality is that from an evolutionary perspective, we don’t know as much about mammals as we do about how birds diverged,” says Nicole Foley of Texas A&M University.

In the past, she explains, many researchers used the fossil record to argue that all real activity in mammals occurred after the mass extinction of the non-avian dinosaurs.

But this huge new collection of mammalian DNA gave Foley and her colleagues a chance to look at it differently, analyzing so-called neutral evolutionary sites, where random changes in the genetic code over time can serve as a clock. .

“With all this data, we can get to a point where we have a much more precise timeline for the diversification of mammals,” says Foley.

What has been seen shows that the earliest mammals walked under the feet of dinosaurs, although mammals had not yet had the opportunity to take to the air.

“Mammal evolution starts slowly in the Cretaceous, but it’s there,” says Foley. “Mammals are created in the Cretaceous.”

These creatures may have been small and found in small numbers, but they were the ancestors of everything from bats to primates, says Bill Murphy, also of Texas A&M. “They only started to look like modern bats and modern primates when the dinosaurs were gone,” he says.

From hibernation to hero dog

Modern mammals share many features, but they also differ in important ways. For example, only a few can hibernate, which Carlson notes is an amazing activity.

“Basically, animals can get very obese, go into a hole, not move much for months on end. And then they lose all the weight and come out and they don’t have blood clots and they don’t have strokes and they don’t have diabetes,” she says.

So one of the first things the researchers did was compare the genetic code of hibernating species to their non-hibernating relatives. “And that led to the discovery of some genes associated with some interesting traits, including aging,” Carlson says.

The researchers also tried to use information in their mammalian DNA collection to see if they could make predictions, such as studying which species might be susceptible to the pandemic coronavirus. Some of their predictions, such as the possibility of deer being affected, actually came true.

One research group at the University of California, Santa Cruz, used this data set along with the genomes of hundreds of modern dogs to try to learn something about a very special dog of the past.

They collected DNA from Balto, a sled dog that helped transport valuable medicine to Alaska during a diphtheria outbreak in 1925. His statue is in New York’s Central Park, and his stuffed body is in the Cleveland Museum of Art.

It turns out that Balto was less inbred than modern dog breeds and may have had adaptations that helped him stay active in harsh conditions. For example, he had gene variants related to things like joint formation and skin thickness.

What people lack

Human uniqueness has long fascinated scientists, and researchers have compared human DNA to that of our close relative, the chimpanzee, as well as that of other species to try to learn what makes the human brain stand out.

Steven Reilly of the Yale School of Medicine says he and his colleagues wanted to know what bits of mammalian DNA have been lost in humans.

“We asked what has happened over millions of years of evolution and that if you look at a dolphin or a dog or a donkey, it’s all there, but then suddenly in humans — poof! I don’t have it,” Reilly explains.

They identified about 10,000 bits of DNA that exist in most other mammals but not humans, and most of these deletions occurred in parts of the genetic code thought to be in regulatory regions, where they can act as dimmer switches that turn other genes up or down.

Many of the human-specific deletions happened near genes involved in brain development, Reilly says, but it wasn’t clear which of them might do something.

So his group performed experiments on a wide range of cell types to see which deletions could actually cause changes in gene activity. They found about 800 cases where the human version of DNA produced different results than the chimpanzee version.

When they took a cell from the human nervous system and added back a deleted piece of DNA, they could sometimes see large-scale effects. For example, they saw that the activity of one gene decreased and this had a cascading effect on the activity of about 30 other genes, ones involved in the formation of a kind of insulation around brain cells, a process called myelination. Human and chimpanzee brains are known to differ significantly in the speed of this myelination (humans are slower).

“The fact that this one change seems to cause all of these genes that would promote myelination to decrease means that this could be one of the genetic links to this known difference between humans and chimpanzees,” Reilly says.

He called it “almost a little humiliating that we don’t have a lot of fancy new bells and whistles to build a brain. It’s mostly the same building blocks that are used to build a chimpanzee brain. Just in a slightly different way.”

Where genetic change accelerates

But some parts of the human genome appear to have evolved particularly quickly. That was the goal of one study that aimed to understand stretches of DNA that are nearly identical in humans but different from all other mammals.

Scientists have searched for these regions in the past, but this new collection of mammalian genomes gives the search new impetus.

It turns out that many regions of accelerated genetic change in humans cause DNA to fold differently than in other primates, says Cathy Pollard, director of the Gladstone Institute for Data Science and Biotechnology in San Francisco. This is important because different types of folding can have a profound effect on what genes are turned on and off and how they all interact.

“DNA is a very long, thin molecule. You can think of it as a thread and imagine taking over a meter of thread and trying to pull it into the nucleus of a cell,” says Pollard. “It doesn’t just randomly pull in and fold. It actually folds in a coordinated way. And the way it folds is predictable from the DNA sequence.”

Many years ago, says Pollard, biologists thought that human genes might be radically different from those of chimpanzees. Instead, they’ve learned that the genes that make the proteins themselves are quite similar, but the way they’re regulated and even packaged in three-dimensional space can vary significantly in people.

“I think it’s important to remember that what makes us human is not one change, but many, many changes,” Carlson says.

What’s more, she says, people have traditionally been very good at studying humans and other primates, “but as we get to know many other species, we know surprisingly little about them and what they can do.”