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The virus that causes COVID-19 may share a common ancestor with bat coronaviruses later
than scientists thought.
But finding the direct ancestor of SARS-CoV-2 is highly unlikely
, the researchers say.
The complete genomes of SARS-CoV-2 and several closely related bat coronaviruses suggest that they shared a common ancestor
decades ago.
But viruses are known to exchange RNA fragments with each other, a process known as recombination, so each part has its own evolutionary history
.
In the latest analysis, presented at the 7th World Congress on Unified Health in Singapore on November 8, scientists compared fragments
of the coronavirus genome.
The analysis revealed that as recently as 2016, some parts of the bat coronavirus shared a common ancestor with SARS-CoV-2 – just 3 years later, the virus appeared in
humans in late 2019.
The study has not been peer-reviewed
.
The discovery narrows the time lag
between the ancestors of SARS-CoV-2, which originated in bats, and the virus's transmission to humans, the researchers said.
However, it cannot explain how SARS-CoV-2's closest ancestor made this leap — an enduring mystery of the pandemic that many scientists believe may have involved an intermediate animal
.
The study highlights how difficult
it will be to find the direct ancestor of SARS-CoV-2 in bats, given the frequency of coronavirus recombination and the time that has passed.
Edward Holmes, an evolutionary virologist at the University of Sydney in Australia, says the chances of finding direct ancestors are "almost zero"
.
Joel Wertheim, a molecular epidemiologist at the University of California, San Diego, said the direct ancestor of SARS-CoV-2 may have formed from several viruses that have been recombinant and mutated
in bats ever since.
Wertheim contributed
to the latest analysis.
Coronavirus sampling of bats may identify virus fragments that are closer than those found so far in known coronaviruses, but may not reveal a direct ancestor
, he said.
Since the beginning of the pandemic, many researchers, especially in Southeast Asia, have been sequencing
coronaviruses found in bats and other mammals.
They also sequenced the coronavirus in older tissue samples stored in freezers, hoping to find the origin
of the pandemic.
But scientists have struggled to find SARS-CoV-2's precursor virus, leading to speculation that the pandemic was sparked by a virus accidentally leaking out of the Wuhan Institute of Virology, located in the city where the
pandemic began.
The lab has been studying related coronaviruses
.
So far, more than a dozen viruses
closely related to SARS-CoV-2 have been isolated from bats and pangolins.
To determine their relationship to SARS-CoV-2, researchers often compare their entire genomes, which are about 30,000 nucleotides long
.
With this approach, they found that the known close relatives of SARS-CoV-2 are the bat virus BANAL-52, found in Laos, whose genome is 96.
8% identical to that of SARS-CoV-2, and a virus called RaTG13, found in Yunnan, southern China, which has a genome 96.
1% identical
to that of SARS-CoV-2.
There is a 3-4% difference between their genome and that of SARS-CoV-2, suggesting that these viruses have evolved for about 40-70 years
since they shared a common ancestor.
But the researchers say comparing whole-genome sequences ignores the role of
recombination in viral evolution.
Some RNA fragments may be very different from SARS-CoV-2, suggesting that they are more distantly related, while other, much more similar fragments mean they are more closely
related.
To explain the recombination, the researchers compared 18 bat and pangolin viruses closely related to SARS-CoV-2 and spliced them into 27 segments
.
Spyros Lytras, an evolutionary virologist at the University of Glasgow in the United Kingdom, who presented the study in Singapore, said that each fragment — hundreds to thousands of nucleotide sequences — has a different evolutionary history
.
For each fragment, the researchers used a larger subset of 167 related viruses to estimate how long
SARS-CoV-2 shared a common ancestor with bat or animal viruses.
The study was described in an article in the virological.
org discussion forum last month, and co-authors plan to submit it to a journal
early next year.
The analysis revealed that just a few years ago, some fragments shared a common ancestor
with SARS-CoV-2.
Most fragments shared a common ancestor around 2007, but a small fragment about 250 nucleotides long may share a common ancestor in 2016, and another 550 nucleotide-long fragment may share a common ancestor in 2015 – only 3-4 years before
SARS-CoV-2 appeared in humans.
The youngest fragments come from bat samples
from Yunnan and Laos.
Given how far these viruses can travel with their bat hosts, the analysis suggests that southern China and Southeast Asia are hotspots for SARS-CoV-2 ancestral regions
, Lytras said.
"It's a smart approach," Holmes said
.
"It gives you the purest signal
of evolutionary time.
" However, he noted that some fragments are quite short, which makes these estimates less reliable because of the limited
number of RNA nucleotides available for comparison.
