Even before the reign of the dinosaurs ended in a mass extinction event some 65 million years ago, mammals had already gained a humble but solid foothold.
This is just one of the results of a careful examination of the DNA of 240 different mammal species, an ambitious effort to understand how hairy and milk-producing mammals, including humans, evolved to have such an astonishing range of sizes, shapes and special abilities.
Scientists know about 6,500 species of living mammals, which inhabit virtually every environment on Earth, from frigid oceans to high deserts. This international project, called Zoonomia, set out to collect genetic material from the entire mammalian family tree.
Researchers have 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 portion of mammals, but it’s the largest project we’ve ever done this way,” says Elinor Karlsson, director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard, who notes that the 80 % of mammalian families are represented in their collection.
After determining the sequence of chemical “letters” that made up each species’ genetic code, the researchers then “lined up” those sequences so that they could be compared comprehensively. This allowed them to pinpoint which genetic regions had remained unchanged over millions of years of evolution, suggesting that these contain biological instructions essential for making mammals.
They were also able to pinpoint genetic differences between mammalian species, which allowed them to probe the possible genetic basis of unique traits such as the ability to hibernate or an extremely sensitive sense of smell.
“It turns out that there is a strange little South American rodent that nobody seems to know much about that has a huge number of olfactory genes and receptors,” says Karlsson. “It sort of indicates what we can discover when we’re just looking at everything.”
She and her colleagues have now published 11 research reports in the journal Science exhibiting some of their first efforts to understand what exactly, at the genetic level, makes a mammal.
And, interestingly, they found some clues about how a mammal, homo sapiensit evolved to have such a unique brain, the kind of brain that can think mammals and devise complex computational programs to compare and contrast the massive amounts of data throughout this genetic code.
When mammals began to emerge
Scientists have long debated when mammals first appeared on Earth and how and why they began to diversify, eventually settling in almost any possible habitat and ranging in size from tiny bats to enormous whales.
“The reality is that, evolutionarily speaking, we don’t know as much about mammals as we do about how birds differentiated,” says Nicole Foley of Texas A&M University.
In the past, many researchers have used the fossil record to insist that all the real mammalian action occurred after the mass extinction of non-avian dinosaurs, he explains.
But this vast new collection of mammalian DNA has given Foley and his colleagues a chance to look at this in a different way, by analyzing so-called neutral evolution sites, where random changes in the genetic code over time can serve as a sort of of clock. .
“With all this data, we can somehow get to the point where we have a much more accurate timeline for mammalian diversification,” Foley says.
What they saw indicates that early mammals walked under the feet of dinosaurs even though the mammals hadn’t yet had a chance to take off.
“Mammal evolution starts slowly in the Cretaceous, but it’s there,” says Foley. “Mammals are established in the Cretaceous.”
These creatures may have been small and found in low numbers, but they were the predecessors of everything from bats to primates, says Bill Murphy, also of Texas A&M. “They started looking 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 are allowed to hibernate, which Karlsson says is an amazing activity.
“Basically the animals are able to get super obese, climb into a hole, not move much for months and 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,” He says.
That’s why one of the first things the researchers did was compare the genetic code of hibernating species to their non-hibernating relatives. “And that ended up finding some genes involved in some interesting traits, including aging,” says Karlsson.
The researchers also looked to use the information in their mammalian DNA collection to see if they could make predictions, such as exploring which species might be susceptible to the pandemic coronavirus. Some of their predictions, such as the likelihood that deer would be affected, have actually been successful.
A group of researchers at the University of California, Santa Cruz used this data set along with hundreds of modern dog genomes to try to find out something about a very special dog from the past.
They collected DNA from a sled dog named Balto, who famously helped carry precious medicine across Alaska during a diphtheria epidemic in 1925. A statue of him stands in New York City’s Central Park and his stuffed body it is located in a museum in Cleveland.
It turns out that Balto was less inbred than dogs of modern breeds and perhaps had adaptations that helped him stay active in harsh conditions. For example, he had variations in genes related to things like joint formation 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 close relative, the chimpanzee, as well as other species to try to understand what distinguishes the human brain.
Steven Reilly of the Yale School of Medicine says he and his colleagues wanted to know which bits of basic mammalian DNA had been lost in humans.
“We wondered what has been over millions of years of evolution and that if you look at a dolphin or you look at a dog or you look at a donkey, it’s all there, but then suddenly in humans poof! I don’t have it,” explains Reilly .
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 switches. weaker ones that turn the activity of other genes up or down.
Many of the human-specific deletions occurred near genes related to brain development, Reilly says, but it wasn’t clear which of them might actually be doing anything.
So his group then ran experiments across a range of cell types, to see which deletions might actually produce changes in gene activity. They found about 800 cases where the human version of the DNA produced a different result than the chimpanzee version.
When they took a cell from a human nervous system and added a fragment of deleted DNA to it, they could sometimes see wide-ranging 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, associated with the formation of a kind of insulation around brain cells, a process called myelination. Human and chimpanzee brains are known to differ markedly in the rate of this myelination (humans go slower).
“The fact that this change appears to cause a reduction in all of these myelination-promoting genes means that this could be one of the genetic links toward this known difference between humans and chimpanzees,” Reilly says.
He called it “almost a little humbling that we don’t have a lot of fancy new bells and whistles for building a brain. It largely uses the same building blocks that go into making a chimpanzee brain. Just in a slightly different way.”
Where genetic changes accelerate
But some parts of the human genome appear to have evolved particularly rapidly. That was the goal of a study that wanted to understand DNA traits that are nearly identical among humans, but differ from all other mammals.
Scientists have searched for these regions in the past, but this new collection of mammalian genomes gives that search new power.
It turns out that many regions 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. This is important because different types of folding can greatly influence which genes are turned on and off, and how they interact.
“DNA is a very long, thin molecule. You can think of it as a string and imagine taking more than a meter of string and trying to squeeze it into the nucleus of a cell,” says Pollard. “It doesn’t just get crumpled and folded in a random way. It actually folds in a concerted way. And how it folds is predictable from the DNA sequence.”
Many years ago, Pollard says, biologists thought human genes might be radically different from chimpanzee genes. Instead, what they learned is that the protein-making genes themselves are quite similar, but how they are regulated and even packaged in three-dimensional space could be profoundly altered in humans.
“I think it’s important to remember that what makes us human is not one change, but many, many changes,” says Karlsson.
Also, he says, humans have traditionally been very good at studying humans and other primates, “but when you go out into many other species, we know surprisingly little about them and what they can do.”