Raul Rabadan: Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2 (Covid-19 symposium)

Summary by: Arooba Ahmed (CC '23)

     The virus is currently evolving through two mechanisms. The first way is mutation, where there is one substitution in the virus every couple of weeks. They can track the evolution of the virus around the world using the GISAID database with sequences and phylogenetic trees. Interestingly, the virus looks different in different parts of the world. 
     Another way in which the virus evolves is through recombination, where coinfection with a different virus generates a chimera (parts are mixed). Coronaviruses in particular acquire new abilities quickly. The first record of Sars-Cov-2 was in December. Within the first two weeks it had been sequenced. One of the first papers on this virus took the whole genome and compared it with other viruses. 
    Some other viruses were found to be very similar, which suggests a common origin. There was perhaps a single introduction in November 2019 where all the viruses were similar, but ended up diversifying. What is interesting is that although the Sars-Cov-2 virus may look distantly related to the SARS 2002 virus, they are not actually distant. It depends rather on how you look at the genome. Dr. Rabadan shows a tanglegram where the whole genome is not very similar, but the receptor binding domains (which determine viral entry into the cell) are very similar. His group also found that this virus can recombine everywhere in the genome, but in some places the recombinations are much greater. For example, they found many more recombinations near spike protein. The spike protein is the point of entry and determines host range for the virus.
    They also took the data and tried to figure out the timing for when the evolution happened. This virus is related to the one in pangolins which was circulating last year, as determined by looking at just the receptor binding domain region. The closest virus to SARS-Cov-2 in terms of the whole genome is a strain that was isolated in bats around 2014. 
    Looking at the whole genome, there are 2 branches. One branch contains SARS and the other contains Sars-Cov-2. 10-15 years ago there was recombination between the two and there were lineage specific mutations that created what it is today. These mutations allowed it to bind to the ACE2 receptor in humans.