How Omicron's Mutations Allow It To Thrive - The New York Times

Thirteen of Omicron’s mutations should have hurt the variant’s chances of survival.

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-dominating variant came to be.

When the Omicron variant took off in southern Africa in November, scientists were taken aback by its genetic makeup.

Whereas earlier variants had differed from the original Wuhan version of the coronavirus by a dozen or two mutations, Omicron had 53 — a shockingly large jump in viral evolution.

They found that 13 of those mutations were rarely, if ever, found in other coronaviruses, suggesting they should have been harmful to Omicron.

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

It could make the virus stick more tightly to cells, for example, or make it replicate faster.

And then came Omicron, with over twice as many mutations.

As soon as Omicron came to light, Dr.

But if it is rare or missing altogether, that’s typically a sign that it is harmful to the virus, preventing it from multiplying.

What makes these 13 mutations all the more intriguing is that they’re not randomly sprinkled across Omicron’s spike.

And each of those three areas play a big part of what makes Omicron unique.

Two of the clusters change the spike near its tip, making it harder for human antibodies to stick to the virus and keep it out of cells.

This region, known as the fusion domain, swings into action once the tip of the spike has hooked onto a cell, enabling the virus to deliver its genes inside its new host.

These three regions of the spike seem to have been important for Omicron’s success.

This makes it all the more puzzling that these 13 mutations were so vanishingly rare before Omicron.

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

It could make the virus’s spike protein unstable so that it can’t latch quickly onto a cell, for example.

Pond speculates, until Omicron evolved a spike protein with just the right combination of mutations to allow it to spread supremely well among healthy people.

It’s possible, for example, that the 13 spike mutations offer no benefit to Omicron at all.

Instead, some of the other spike mutations could be making Omicron successful, and the 13 are just along for the ride.