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

Before the mass extinction event ended the reign of the dinosaurs about 65 million years ago, mammals had already established a humble but strong foothold.

It’s just one of the findings from a close examination of DNA from 240 different mammals, an ambitious attempt to understand how hairy, milk-producing mammals — including humans — evolved to have such an astonishing range of sizes, shapes and special abilities.

Scientists know of about 6,500 living mammal species, living in nearly every environment on Earth—from frigid oceans to high deserts. This international project, called Zoonomia, is set to collect genetic material from the entire mammal family tree.

The researchers obtained DNA from all kinds of mammals, such as caribou, armadillos, bats and bison. Their genetic menagerie eventually included 52 endangered species, such as giant otters and Amazon river dolphins, as well as primates such as chimps and humans.

“We’re still only looking at a small subset of mammals, but this is the largest project we’ve ever done this way,” says Elinor Carlson, director of the Vertebrate Genomics Group at MIT and Harvard’s Broad Institute, who notes. That 80 percent of the mammal families are represented in their collections.

After determining the sequence of chemical “letters” that make up each species’ genetic code, the researchers then “aligned” those sequences so they could be broadly compared. It allows them to discover which genetic regions have remained unchanged over millions of years of evolution, suggesting that they contain the biological instructions needed to create mammals.

They were also able to tease apart genetic differences between mammal species, which allowed them to investigate the possible genetic basis of unique traits such as the ability to hibernate, or a highly sensitive sense of smell.

“It turns out there’s a weird little South American mouse that nobody seems to know much about that has a huge number of olfactory genes and receptors,” says Carlson. “It points out what we can find when we’re just looking at everything.”

She and her colleagues have now published 11 research reports in the journal Science which represent some of his first attempts to understand, at the genetic level, what makes a mammal.

And interestingly, they found some clues about how a mammal. Homo sapiensSuch a unique brain has evolved—the kind of brain that can think in mammals and devise complex computational programs to compare and contrast the vast amounts of data in all this genetic code.

When the mammals started to emerge

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

“The reality is, from an evolutionary standpoint, 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, many researchers have used the fossil record to insist that all real action for mammals occurred after the mass extinction of non-avian dinosaurs, she explains.

But this vast new collection of mammalian DNA gave Foley and his colleagues a chance to look at this differently by analyzing so-called neutrally-evolving sites, where random changes in the genetic code over time can act as a kind of clockwork. .

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

What they saw suggests that early mammals were walking under the feet of dinosaurs—even though mammals hadn’t really had a chance to take off yet.

“Mammal evolution kind of starts slowly in the Cretaceous, but it’s there,” says Foley. “Mammals established in the Cretaceous.”

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

From Hibernation to Hero Dog

Today’s mammals share many characteristics, but they also differ in important ways. For example, only some can hibernate, which Carlson notes is a remarkable activity.

“Basically animals can get super obese, climb into a hole, not move at all for months. And then they lose all that weight and they come out and they don’t have blood clots and they don’t have strokes and they don’t have diabetes. ,” she says.

That’s why one of the first things researchers did was compare the genetic code of hibernating species to their non-hibernating relatives. “And it ended up finding some genes involved in some interesting traits, including aging,” Carlson says.

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

A group of researchers at the University of California, Santa Cruz used this dataset — along with hundreds of genomes from modern dogs — to try to discover something about a very special dog of the past.

They collected DNA from a sled dog named Balto, who famously helped transport valuable medicine to Alaska during a diphtheria outbreak in 1925. A statue of him is in New York City’s Central Park, and his stuffed body is in a Cleveland museum.

It turns out that Balto was less inbred than modern dog breeds, and probably had adaptations that helped him stay active in harsh conditions. For example, he had variations in genes related to things like joint structure and skin thickness.

What is missing in humans?

The uniqueness of humans has long fascinated scientists, and researchers have compared human DNA with that of our closest relative, the chimpanzee, as well as other species, trying to learn what makes the human brain unique.

Steven Reilly of the Yale School of Medicine says he and his colleagues wanted to know which bits of DNA from basic mammals have been lost in humans.

“We asked, what has been there over millions of years of evolution, and if you look at dolphins or you look at dogs or you look at donkeys, it’s all there, but then suddenly in humans—poof!—we don’t have it,” Reilly explains.

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

There have been human-specific deletions near genes related to brain development, Reilly says, but it wasn’t clear which of them might actually do something.

So his group then performed experiments in a wide range of cell types, to see which deletions could actually change gene activity. They found about 800 cases where the human version of the DNA produced a different result than the chimp version.

When they take a cell from the human nervous system and delete one of the DNA they can sometimes see far-reaching effects. For example, they found that the activity of one gene decreased, and this affected the activity of about 30 other genes involved in the formation of a type of insulation around brain cells – a process called myelination. The brains of humans and chimps are known to differ markedly in the speed of this myelination (humans go slower).

“The fact that this one change causes a reduction in all of these genes that would promote myelination means that this could be one of the genetic links to the known difference between humans and chimps,” Reilly says.

He called it “almost a little condescending that we don’t have a lot of new fancy bells and whistles to make a brain. It uses mostly the same building blocks that go into making a chimp brain. Just a little differently.”

where genetic changes are accelerated

But some parts of the human genome seem to have evolved particularly quickly. It was the focus of a study that sought 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 new impetus to those searches.

It turns out that many areas of accelerated genetic change in humans cause DNA to fold differently than in other primates, says Katie Pollard, director of the Gladstone Institute of Data Science and Biotechnology in San Francisco. That’s important because different types of folding can dramatically affect which genes are turned on and off and how they all interact.

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

Many years ago, Pollard says, biologists thought that human genes might be radically different from chimp genes. Instead, what they’ve learned is that the protein-producing genes themselves are very similar, but the way they’re regulated and even packed up in three-dimensional space can vary profoundly among humans.

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

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