Leap from bats to humans was easy for SARS-CoV-2 — study
SARS-CoV-2, the virus that causes COVID-19, is part of a lineage of “generalist” viruses that infect many mammal species.
Its transition to humans was relatively easy, and there were few significant changes in its genome during the early months of the pandemic.
By the end of 2020, however, there was increased selection pressure on the virus as a result of the large numbers of people who had contracted it and were immune.
As the proportion of vaccinated individuals rises, selection pressure on the virus to evade its hosts’ immune defenses will increase further.
Health officials quickly traced the initial outbreak of COVID-19 in December 2019 to a seafood market in the Chinese city of Wuhan.
Exactly how the virus passed from its original animal host into humans remains a mystery, however.
Viruses closely related to SARS-CoV-2 — the virus that causes COVID-19 — have been found in horseshoe bats and pangolins, but previous research suggests that its lineage diverged from theirs several decades ago.
Scientists are keen to find out more about the origins of the virus, because it will help them assess the risk of similar viruses emerging that could cause future pandemics.
Two key questions are:
How much evolutionary adaptation was required to make the jump into humans?
How fast did the virus evolve once it had established in the human population?
According to new research by scientists in the United States, the United Kingdom, and Belgium, the transition from bats to people was one small step for the virus.
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The researchers have published their results in the journal PLOS Biology.
The scientists drew upon their experience of tracing the evolutionary origins of HIV and other viruses.
They scoured the genomes of more than 130,000 samples of SARS-CoV-2 collected between December 2019 and October 2020 for signs of evolutionary adaptations. They then contrasted these with the molecular signatures of adaptation in 69 related bat viruses.
Their analysis suggests that most of the adaptations that allowed the SARS-CoV-2 lineage to jump from bats to humans and spread across the world arose in bats many years ago.
They note that many sarbecoviruses — which are the group of bat and pangolin viruses to which SARS-CoV-2 belongs — are “generalists.” This means that they have adaptations that allow them to skip from one mammalian host species to another relatively easily.
The research also revealed that there were few evolutionarily significant changes in the genome of the virus during the first 11 months of the pandemic. This implies that the virus was already well adapted to its new host and could “hit the ground running.”
“What has been so surprising is just how transmissible SARS-CoV-2 has been from the outset,” says co-lead author Prof. Sergei Pond from the Institute for Genomics and Evolutionary Medicine at Temple University in Philadelphia, PA.
“Usually viruses that jump to a new host species take some time to acquire adaptations to be as capable as SARS-CoV-2 at spreading, and most never make it past that stage, resulting in dead-end spillovers or localized outbreaks,” he adds.
The researchers explain that this does not mean there were no changes in the virus’s genome over this period.
Random mutations occur in the genetic sequences of viruses all the time. Mutations with negative consequences for the virus are weeded out by natural selection, whereas beneficial ones proliferate.
However, “neutral” mutations that are neither beneficial nor detrimental for the virus can persist by default.
There were some significant changes during this period, say the researchers. For example, a mutation called D614G that affected its spike protein allowed the virus to infect host cells more easily.
This made the virus more transmissible, but it did not appear to make the disease any more severe.
The majority of mutations that arose during this early phase of the pandemic were neutral, however.
“This stasis can be attributed to the highly susceptible nature of the human population to this new pathogen, with limited pressure from population immunity, and lack of containment, leading to exponential growth, making almost every virus a winner,” says co-first author Dr. Oscar MacLean from the University of Glasgow Centre for Virus Research (CVR) in the U.K.
This free-for-all appeared to end in late 2020 with the emergence of new “variants of concern,” such as the U.K. and South African strains.
A growing proportion of the human population became immune to the virus as a result of previous infections, which increased selective pressure on the virus and accelerated its evolution.
Mutations that allowed the virus to spread — despite increasing immunity within the population — began to come to the fore.
“The reason for the ‘shifting of gears’ of SARS-CoV-2 in terms of its increased rate of evolution at the end of 2020, associated with more heavily mutated lineages, is because the immunological profile of the human population has changed,” says senior author Prof. David L. Robertson from CVR.
In addition, some significant mutations may have had time to evolve during infections that became long-term and chronic — for example, in patients with weakened immune systems.
The vaccines currently in use were designed to provoke a strong immune response to the strain of the virus that was prevalent at the start of the pandemic.
As time passes, and the evolution of the virus gathers pace, there is an increased risk that the virus could mutate in a way that would allow it to evade immunity from previous infection or vaccination with current vaccines.
“The first race was to develop a vaccine. The race now is to get the global population vaccinated as quickly as possible,” says Prof. Robertson.
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