The coronavirus is mutating—but what determines how quickly?

Though not technically alive, viruses mutate and evolve similar to living cells, producing new variants all the time.

Published 5 Feb 2021, 22:21 GMT

Without genetic mutations, there would be no humans. There wouldn’t be any living beings at all—no mammals, insects, or plants, not even bacteria.

These tiny errors, which can happen at random each time a cell or virus copies itself, provide the raw materials for evolution to take place. Mutations create variation in a population, which allows natural selection to amplify the traits that help creatures thrive—stretching a giraffe’s long neck to reach high leaves, or camouflaging caterpillars like poo to evade birds’ notice.

Amid a pandemic, however, the word “mutation” strikes a more ominous note. Viruses, though not technically alive, also mutate and evolve as they infect a hosts’ cells and replicate. The resulting tweaks to the virus’s genetic code could help it more readily hop between humans or evade the defences of the immune system. Three such mutants of the virus SARS-CoV-2 have prompted experts to advocate for redoubled efforts to curb the coronavirus’s spread.

But these three versions of the virus are just a few among thousands of SARS-CoV-2 variants that have sprung up since the pandemic began. “We are creating variants like gangbusters right now because we have so many humans infected with SARS CoV-2,” says Siobain Duffy, a vial evolutionary biologist at Rutgers School of Environmental and Biological Sciences.

Many of these variants have since vanished. So why do some versions disappear, and why does the virus change in the first place? What mechanisms play puppet master for evolving viruses?

“The virus will change because that’s the underlying biology,” says Simon Anthony, a virologist working in infectious diseases at the University of California, Davis. “The question then becomes, are those changes significant to us?”

Replicating genetic codes

A successful virus is one that makes more of itself. But these tiny entities can’t do much on their own. Viruses are essentially coils of genetic material stuffed into a protein shell that’s sometimes blanketed in an outer envelope. In order to replicate, they must find a host. The virus binds to its target’s cells, injecting genetic material that hijacks the host’s cellular machinery to make a new generation of viral progeny.

But each time a new copy is made, there’s a chance that an error, or mutation, will occur. Mutations are like typos in the string of “letters” that make up a strand of DNA or RNA code.

The majority of mutations are harmful to a virus or cell, limiting the spread of an error through a population. For example, mutations can tweak the building blocks of proteins encoded in the DNA or RNA, which alters a protein’s final shape and prevents it from doing its intended job, Duffy explains.

“It doesn’t make the nice little curlicue alpha-helices it’s supposed to,” she says of a common structure found in proteins. “It doesn’t make the nice folded sheets it's supposed to.”

Many other mutations are neutral, having no effect on how efficiently a virus or cell reproduces. Such mutations sometimes spread at random, when a virus carrying the mutation spreads to a population that hasn’t been exposed to any variants of the virus yet. “It’s the only kid on the block,” Anthony says.

However, a select few mutations prove useful to a virus or cell. For example, some changes could make a virus better at jumping from one host to the next, helping it outcompete other variants in the area. This was what happened with the SARS-CoV-2 variant B.1.1.7 that was first identified in the United Kingdom but has now spread to dozens of countries around the world. Scientists estimate the variant is roughly 50 percent more transmissible than past forms of the virus, giving it an evolutionary edge.

The pace of evolution

Mutations may happen randomly, but the rate at which they occur depends on the virus. The enzymes that copy DNA viruses, called DNA polymerases, can proofread and fix errors in the resulting strings of genetic letters, leaving few mutations in each generation of copies.

But RNA viruses, like SARS-CoV-2, are the evolutionary gamblers of the microscopic world. The RNA polymerase that copies the virus’s genes generally lacks proofreading skills, which makes RNA viruses prone to high mutation rates—up to a million times greater than the DNA-containing cells of their hosts.

Coronaviruses have a slightly lower mutation rate than many other RNA viruses because they can do some light genetic proofreading. “But it’s not enough that it prevents these mutations from accumulating,” says virologist Louis Mansky, the director for the Institute for Molecular Virology at the University of Minnesota. So as the novel coronavirus ran amok around the world, it was inevitable that a range of variants would arise.

The true mutation rate of a virus is difficult to measure though. “Most of those mutations are going to be lethal to the virus, and you’ll never see them in the actively growing, evolving virus population,” Mansky says.

Instead, genetic surveys of sick people can help determine what’s known as the fixation rate, which is a measure of how often accumulated mutations become “fixed” within a viral population. Unlike mutation rate, this is measured over a period of time. So the more a virus spreads, the more opportunities it has to replicate, the higher its fixation rate will be, and the more the virus will evolve, Duffy says.

For SARS-CoV-2, scientists estimate that one mutation becomes established in the population every 11 days or so. But this process may not always happen at a steady pace.

In December 2020, the variant B.1.1.7 caught scientists’ attention when its 23 mutations seemed to suddenly crop up as the virus rampaged through Kent. Some scientists speculate that a chronically ill patient provided more opportunities for replication and mutation, and the use of therapies such as convalescent plasma may have pressured the virus to evolve. Not every change was necessarily useful to the virus, Duffy notes, yet some mutations that emerged allowed the variant to spread rapidly.

The wide world of viruses

Mutations drive evolution, but they are not the only way that a virus can change over time. Some viruses, like influenza, have other ways to increase their diversity.

Influenza is made up of eight genetic segments, which can be rearranged—a process called reassortment—if multiple viruses infect a single cell to replicate at the same time. As the viral progeny are packaged into their protein capsules, the RNA segments from the parent viruses can be mixed and matched like viral Lego. This process can cause rapid shifts in the viral function. For example, reassortments of flu strains circulating in pigs, birds, and humans led to the 2009 H1N1 flu pandemic.

Unlike influenza, however, coronaviruses possess no physical segmentation to undergo reassortment. Coronaviruses can experience some shifts in function through a process known as recombination, when segments of one viral genome are spliced onto another by the enzyme making the viral copy. But researchers are still working to determine how important this process is for SARS-CoV-2’s evolution.

Understanding these evolutionary dynamics of SARS-CoV-2 is vital to ensure that treatments and vaccines keep pace with the virus. For now, the available vaccines are effective in preventing severe disease from all the viral variants.

And the study of SARS-CoV-2’s evolution could help answer another looming question: Where did the virus come from? While the disease likely originated from bats, there are still missing chapters in the tale of SARS-CoV-2’s leap to human hosts. Filling in these blanks could help us learn how to protect ourselves in the future.

“As a society, globally, we don’t want this to happen again,” Mansky says.

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