Omicron’s Fundamental Evolution Explained

covid

An image provided by the National Institutes of Health shows a colored scanning electron micrograph of a cell infected with a coronavirus. National Institutes of Health via The New York Times

As nurses and doctors struggle with a record-breaking wave of Omicron cases, evolutionary biologists are engaged in a struggle of their own: figuring out how this world-dominated version came to be.

when The Omicron variant flew over southern Africa in November, with scientists astonished by its genetic makeup. While the earlier variants differed from the original Wuhan version of the coronavirus by a dozen or two mutations, Omicron had 53 – a startlingly big leap in viral evolution.

In Study Posted Online Last WeekAn international team of scientists deepened the mystery. They found that 13 of those mutations were rarely, if ever, found in other coronaviruses, suggesting they must have been deleterious to Omicron. Instead, when acting in concert, these mutations appear to be important for some of the most essential functions of the omicron.

Now researchers are trying to figure out how Omicron defied normal laws of evolution and used these mutations to become such a successful vector of disease.

“Here’s a secret that one has to find out,” said Darren Martin, a virus expert at the University of Cape Town who worked on the new study.

Mutations are a regular part of a coronavirus’s existence. Every time a virus replicates inside a cell, there is little chance that the cell will make an error copy of its gene. Many of those mutations will make the new virus defective and unable to compete with other viruses.

But a mutation can also improve a virus. For example, it can make the virus stick to cells more strongly, or make it replicate faster. Viruses that acquire beneficial mutations can outnumber others.

For much of 2020, scientists found that different lineages of coronaviruses around the world gradually carried a handful of mutations. The process of development was slow and steady till the end of the year.

In December 2020, British researchers were shocked to discover a new variant in England containing 23 mutations not found in the original coronavirus isolated in Wuhan, China, a year earlier.

That version, later renamed the Alpha, soon gained worldwide dominance. During 2021, other rapidly spreading variants emerged. While some remained limited to certain countries or continents, the delta version, with 20 specific mutations, removed the alpha and became dominant over the summer.

And then omicron came, with more than twice the mutation.

As soon as Omicron came to light, Martin and his colleagues began to reconstruct the radical evolution of the variant by comparing its 53 mutation with other coronaviruses. Some of the mutations were shared by omicron, delta and other forms, suggesting that they arose multiple times and that natural selection favored them over and over again.

But the scientists found a different pattern when they looked at the “spike” protein that studs the surface of the oomicron and allows it to be carried to cells.

Omicron has 30 mutations in its spike gene. The researchers found that 13 of them were extraordinarily rare among other coronaviruses – even their distant viral cousins ​​found in bats. Some of the 13 never-before-seen millions of coronavirus genomes scientists have sequenced during the pandemic.

If a mutation is beneficial to the virus, or even neutral, scientists would expect it to appear more frequently in samples. But if it is rare or missing entirely, it is usually a sign that it is harmful to the virus, preventing it from multiplying.

“When you see that pattern, it’s telling you something very loudly and very clearly,” Martin said. “Anything that sustains the change at those sites is probably going to be faulty and won’t live and die for very long.”

And yet Omicron was flouting that argument. “Omicron wasn’t going to end at all,” Martin said. “It was just flying like we’ve never seen before.”

What makes these 13 mutations all the more interesting is that they are not randomly spliced ​​into the oomicron’s spike. They form three clusters, each replacing a small portion of the protein. And each of those three regions plays a big part in what makes Omron unique.

The two clusters replace the spike near its tip, making it harder for human antibodies to stick to the virus and keep it out of cells. As a result, Omicron is good at infecting even people who have antibodies from vaccinations or previous COVID infections.

The third group of mutations alters the spike closer to its base. This region, known as the fusion domain, once the tip of the spike is anchored to a cell, enables the virus to deliver its genes inside its new host.

Typically, coronaviruses use fusion domains to merge with the cell’s membrane. Their genes can then float into the depths of the cell.

But Omicron’s fusion domain usually does something different. Instead of being absorbed into the cell membrane, the entire virus is swallowed into a sort of cellular sink hole, which closes to form a bubble inside the cell. Once the virus is imprisoned inside the bubble, it can open up and release its genes.

This new route of infection may help explain why Omicron is less severe than Delta. Cells in the upper airway can easily swallow the omicron in a bubble. But deep in the lungs, where COVID can be life-threatening, coronaviruses have to fuse into cells, which Omicron doesn’t do well.

These three regions of the spike appear to be critical to Omicron’s success. This makes it all the more puzzling that these 13 mutations had disappeared so long before Omicron.

Martin and his colleagues suspect the cause is “epistasis”: an evolutionary phenomenon that can make mutations harmful on their own but beneficial when combined.

Omicron may have turned a batch of 13 bad mutations to his advantage by evolving under unusual circumstances. One possibility is that it originated after a sustained period of time inside the body of a person with a particularly weakened immune system, such as an HIV patient. People with chronic COVID-19 infection may become evolutionary laboratories, hosting multiple generations of coronaviruses.

Development may play out differently in such a host, as it occurs every few days or weeks from one healthy individual to another.

“Now it’s stuck in this one person, so all of a sudden it’s doing things it normally wouldn’t,” said Sergei Pond, an evolutionary biologist at Temple University and author of the new study.

Since an immunocompromised host does not produce many antibodies, many viruses are left to spread. And new mutant viruses with opposing antibodies can multiply.

A mutation that allows the virus to evade antibodies is not necessarily beneficial. For example, it can make the virus’s spike protein unstable so that it cannot bind to a cell as quickly. But inside someone with a weakened immune system, the virus may be able to acquire a new mutation that makes the spike stable again.

Similar mutations could have built up on themselves repeatedly in the same individual, Pond speculated, until Omicron developed a spike protein with the right combination of mutations to make it well-disseminated among healthy people. be allowed.

“It certainly sounds plausible,” said Sarah Otto, an evolutionary biologist at the University of British Columbia who was not involved in the study. But she said scientists still need to run experiments to rule out alternative explanations.

It is possible, for example, that 13 spike mutations do not benefit the omicron at all. Instead, some other spike mutation may have made Omicron a success, and 13 are just along for the ride.

“I would be cautious about interpreting the data to indicate that all of these previously deleterious mutations are favorably favored,” Otto said.

Pond also acknowledged that there are still some big gaps in his hypothesis. For example, it is unclear why, during a chronic infection, Omicron would have benefited from its new “bubble” method for entering cells.

“We lack imagination,” Pond said.

James Lloyd-Smith, a disease ecologist at the University of California, Los Angeles, who was not involved in the study, said the research has shown how difficult it is to recreate the evolution of viruses, even one that recently was born. “Nature is certainly playing its part to keep us humble,” he said.

This article is originally from . appeared in the new York Times,

Leave a Comment