As nurses and doctors struggle with a record-breaking wave of Omicron cases, evolutionary biologists are trying to figure out how this world-dominating variant came to be.
Scientists were taken aback by the Omicron variant's genetic makeup when it took off in southern Africa. Omicron had 53 different variations of the coronaviruses, compared to the original version of the coronaviruses which had a dozen or two variations.
An international team of scientists further deepened the mystery in a study posted online last week. They found that 13 of them were rare in other coronaviruses, suggesting they should have been harmful to Omicron. Some of Omicron's most essential functions appear to be key to some of the mutations.
The Omicron variant has 30 changes in the gene. Other coronaviruses have 13 of those mutations that are extremely rare.
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The spike tip can grab human cells if it swings open, exposing four different variations of the bug.
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Omicron is able to bind more tightly to human cells, and also evade some antibodies that target this region.
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Omicron might be able to get more easily into human cells.
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When the spike tip swings open, there are four changes that can be seen.
CLUSTER 2
Omicron is able to bind more tightly to human cells, and also evade some antibodies that target this region.
CLUSTER 3
Omicron might be able to get more easily into human cells.
CLUSTER 1
When the spike tip swings open, there are four changes that can be seen.
CLUSTER 2
Omicron is able to bind more tightly to human cells, and also evade some antibodies that target this region.
CLUSTER 3
Omicron might be able to get more easily into human cells.
The researchers are trying to figure out how Omicron was able to become such a successful cause of disease.
There is a mystery here that someone has to figure it out, according to a researcher who worked on the new study.
A coronaviruses existence is a regular part of its existence. There is a small chance that a cell will create a flawed copy of its genes when a virus is present. New viruses would not be able to compete with other viruses because of the many defects in them.
A virus can be improved by a genetic change. It could make the virus stick more tightly to the cells. Viruses that have a beneficial trait may be better than others.
Scientists found that different coronaviruses around the world picked up a number of changes over the course of 2020. The evolutionary process was slow and steady until the end of the year.
In December 2020, British researchers discovered a new variant of the coronaviruses in England carrying 23 different genes not found in the original one.
Alpha was the variant that swept to dominance worldwide. Other fast-spreading variant emerged over the course of the year. Alpha was ousted by the Delta variant, which had 20 distinctive mutations, and became dominant over the summer.
Omicron had over twice as many changes. The variant's radical evolution was reconstructed by comparing it to other coronaviruses. Natural selection favored the Omicron, Delta and other variants over and over again, according to the shared mutations.
The scientists found a different pattern when they looked at the Omicron spike, which allows it to latch on to cells.
Omicron's spike gene has 30 defects. 13 of them were extremely rare in other coronaviruses. Some of the 13 had never been seen before in the millions of coronaviruses genomes.
Scientists would expect a positive change in the virus to show up more often in the samples. If it is rare or missing, that is a sign that it is harmful to the virus.
It's telling you something loud and clear when you see that pattern.
It was taking off like nothing we had ever seen.
The 13 mutations are not randomly sprinkled across Omicron's spike. Three clusters form, each altering a small portion of the protein. Omicron is unique because of the three areas.
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. Omicron is good at infecting people who have been exposed to Covid.
The spike is closer to its base after the third cluster of mutations. Once the tip of the spike hooks onto a cell, the fusion domain swings into action, allowing the virus to deliver its genes inside the host.
The fusion domain is used by coronaviruses to combine with a cell. Their genes can be deposited into the depths of the cell.
Omicron's fusion domain does something different. Rather than merging into the cell, the virus gets swallowed up in a sink hole and forms a bubble inside the cell. The virus can break open once it is inside the bubble.
Omicron is less severe than Delta because of this new pathway to infections. The cells in the upper airway are able to swallow bubbles. Covid can cause life-threatening damage in the lungs, and Omicron doesn't do well there.
The three regions of the spike seem to have been important in Omicron's success. This makes it even more puzzling that these 13 genes were so rare before Omicron.
Epistasis is an evolutionary phenomenon that can cause certain types of changes to be harmful on their own, but beneficial when combined.
Omicron may have been able to evolve under unusual conditions. One possibility is that it came from a person with a weak immune system, such as an H.I.V. patient. People with chronic Covid infections can host many generations of coronaviruses.
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Sergei Pond is an evolutionary biologist at Temple University.
Many viruses are left to spread because the host doesn't produce a lot of antibodies. There are new viruses that are resistant to the antibodies.
It isn't necessarily beneficial to have a virus that can evade the immune system. It could make the spikeProtein unstable so that it can be latched onto a cell quickly. A weak immune system may allow a viruses to gain a new version of the spike-reversing mutation.
Dr. Pond theorizes that Omicron could have built upon themselves again and again if they had the right combination of mutations.
Sarah Otto, an evolutionary biologist at the University of British Columbia, was not involved in the study. She said scientists needed to run experiments to rule out alternative explanations.
It is possible that the 13 spike mutations do not benefit Omicron at all. Some of the other spike mutations could be making Omicron successful, and the 13 are just along for the ride.
Dr. Otto said that he would be cautious about interpreting the data to indicate that all of the previously deleterious genes have been changed.
Dr. Pond acknowledged that his hypothesis still has some big gaps. It is not clear why Omicron would have gained an advantage from its new method of getting into cells.
Dr. Pond said that we lack imagination.
James Lloyd-Smith, a disease ecologist at U.C.L.A., said that the research showed how hard it is to reconstruct the evolution of a virus.
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