Human proteins force harmful mutations in the new coronavirus. Still, because of natural selection, it resists and thrives.
Scientists at the University of Bath in England found that mutations in the new coronavirus appear to be driven by human proteins that degrade it, but natural selection allows the microorganism to recover. The discovery was shared earlier this week in the journal Molecular Biology and Evolution.
All organisms undergo mutations, which are usually random processes that occur due to DNA copy errors. In the case of Sars-CoV-2, however, this process seems to be influenced by human proteins, as a defense mechanism to degrade the virus.
The team analyzed about 15,000 genomes of the new coronavirus and identified more than 6,000 mutations. They analyzed how much each of the four nitrogenous bases (called A, C, U, or G) that make up the virus’s genetic code had mutated and found a very high rate of U-related mutations.
“I have looked at mutational profiles for many organisms and they all show some sort of bias, but I’ve never seen one as strong and strange as this,” said Laurence Hurst, director of the Milner Centre for Evolution at the University of Bath, and co-author of the study.
In particular, scientists have found that the mutation often generates neighboring UU pairs from the original CU and UC sequence, which may be a result of the virus’s interaction with the human body.
This is because, according to the team, this type of alteration is related to the human protein APOBEC, which can mutate microorganisms. “It looks like mutation isn’t random, but instead we are attacking the virus by mutating it,” Hurst explained.
By examining the composition of the new coronavirus and comparing parts of its genetic material, the researchers saw evidence that natural selection is actively changing it.
In other words, the microorganisms most capable of surviving this mutation process are those that are thriving.
The team estimated that, after the mutation, 65% of the nitrogenous bases would be U and 40% UU pairs – but in practice, these rates are much lower.
“This could be because the viruses that have too much U in them simply don’t survive well enough to reproduce,” Hurst said. “We estimate that for every 10 mutations that we see, there are another six we never get to see because those mutant viruses are too poor at propagating.”
Several factors can explain the lack of U in the observed microorganisms. In addition to U-rich versions of the virus being less stable, humans have other proteins that target this specific nitrogenous base.
Scientists believe their discovery is important for the development of vaccines against Covid-19.
“Knowing what selection favours and disfavours in the virus is really helpful in understanding what an attenuated version should look like,” Hurst said. “We suggest for example that increasing U content, as APOBEC does within our cells, would be a sensible strategy.”