As Americans anxiously watch variants first identified in the United Kingdom and South Africa spread in the United States, scientists are finding a number of new variants that originated here. More concerning, many of these variants seem to be evolving in the same direction — potentially becoming contagious threats of their own.
In a study posted Sunday, a team of researchers reported seven growing lineages of the novel coronavirus, spotted in states across the country. All of them have evolved a mutation in the same genetic letter.
“There’s clearly something going on with this mutation,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport and a co-author of the new study.
It’s unclear whether it makes the variants more contagious. But because the mutation appears in a gene that influences how the virus enters human cells, the scientists are highly suspicious.
“I think there’s a clear signature of an evolutionary benefit,” Kamil said.
The history of life is full of examples of so-called convergent evolution, in which different lineages follow the same path. Birds gained wings as they evolved from feathered dinosaurs, for example, just as bats did when they evolved from furry, shrew-like mammals. In both cases, natural selection gave rise to a pair of flat surfaces that could be flapped to generate lift — enabling bats and birds alike to take to the sky and fill an ecological niche that other animals could not.
Charles Darwin first recognized convergent evolution by studying living animals. In recent years, virologists have found that viruses can evolve convergently, too. HIV, for example, arose when several species of viruses shifted from monkeys and apes to humans. Many of those lineages of HIV gained the same mutations as they adapted to our species.
As the coronavirus now branches into new variants, researchers are observing Darwin’s theory of evolution in action, day in and day out.
Kamil stumbled across some of the new variants while he was sequencing samples from coronavirus tests in Louisiana. At the end of January, he observed an unfamiliar mutation in a number of samples.
The mutation altered the proteins that stud the surface of the coronavirus. Known as spike proteins, they are folded chains of more than 1,200 molecular building blocks called amino acids. Kamil’s viruses all shared a mutation that changed the 677th amino acid.
Investigating these mutant viruses, Kamil realized they all belonged to the same lineage. The earliest virus in the lineage dated to Dec. 1. In later weeks, it grew more common.
On the evening of his discovery, Kamil uploaded the genomes of the viruses to an online database used by scientists across the world. The next morning, he got an email from Daryl Domman of the University of New Mexico. He and his colleagues had just found the same variant in their state, with the same 677 mutation. Their samples dated to October.
The scientists wondered whether the lineage they had discovered was the only one to have a 677 mutation. Probing the database, Kamil and his colleagues found six other lineages that independently gained the same mutation on their own.
It is difficult to answer even basic questions about the prevalence of these seven lineages because the United States sequences genomes from less than 1% of coronavirus test samples. The researchers found samples from the lineages scattered across much of the country. But they cannot tell where the mutations first arose.
“I’d be quite hesitant to give an origin location for any of these lineages at the moment,” said Emma Hodcroft, an epidemiologist at the University of Bern and a co-author of the new study.
It is also hard to say whether the increase in variants is actually the result of their being more contagious. They might have become more common simply because of all of the travel over the holiday season. Or they might have exploded during superspreader events at bars or factories.
Still, scientists are worried because the mutation could plausibly affect how easily the virus gets into human cells.
An infection begins when a coronavirus uses the tip of the spike protein to latch onto the surface of a human cell. It then unleashes harpoon-like arms from the spike’s base, pulling itself to the cell and delivering its genes.
Before the virus can carry out this invasion, however, the spike protein has to bump into a human protein on the surface of the cell. After that contact, the spike becomes free to twist, exposing its harpoon tips.
The 677 mutation alters the spike protein next to the spot where our proteins nick the virus, conceivably making it easier for the spike to be activated.
Jason McLellan, a structural biologist at the University of Texas at Austin who was not involved in the study, called it “an important advance.” But he cautioned that the way that the coronavirus unleashed its harpoons was still fairly mysterious.“It’s tough to know what these substitutions are doing,” he said. “It really needs to be followed up with some additional experimental data.”
Kamil and his colleagues are starting those experiments, hoping to see whether the mutation does indeed make a difference to infections. If the experiments bear out their suspicions, the 677 mutation will join a small, dangerous club.
Convergent evolution has transformed a few other spots on the spike protein as well. The 501st amino acid has mutated in a number of lineages, for example, including the contagious variants first observed in the United Kingdom and South Africa. Experiments have revealed that the 501 mutation alters the very tip of the spike. That change allows the virus to latch onto cells more tightly and infect them more effectively.
Scientists anticipate that coronaviruses will converge on more mutations that give them an advantage — against not only other viruses but also our own immune system. But Vaughn Cooper, an evolutionary biologist at the University of Pittsburgh and a co-author of the new study, said lab experiments alone would not be able to reveal the extent of the threat.
To really understand what the mutations are doing, he said, scientists will need to analyze a much bigger sampling of coronaviruses gathered from across the country. But right now, they can look at only a relatively meager number of genomes collected by a patchwork of state and university labs.
“It’s ridiculous that our country is not coming up with a national strategy for doing surveillance,” Cooper said.