BREAKING! Comparative Phylogenomics Study Indicates that SARS-CoV-2 Could Have Originated From Guangdong and Not Wuhan Three Months Earlier

SARS-CoV-2: Genomic researchers from the department of molecular biology and genetics, faculty of science, Sivas Cumhuriyet University-Turkey have done a detailed comparative phylogenomics study of various SARS-CoV-2 sequencings and their research findings indicate that the SARS-CoV-2 coronavirus most likely originated from Guangdong province and not Wuhan as originally though and that the coronavirus was already around about 3 months earlier than previously though.


 
The research findings that is yet to have been peer reviewed is published in the site: Preprints. https://www.preprints.org/manuscript/202005.0332/v2
 
Interestingly certain aspect of their findings in terms of the evolution of the SARS-CoV-2 coronavirus also resonates with another study done by Canadian researchers from the University of Calgary. https://www.thailandmedical.news/news/breaking-the-sars-cov-2-coronavirus-could-have-been-evolving-for-the-last-6-years-according-to-canadian-phylogenetic-studies
 
It should be noted that Guandong province is the largest centre for the trade of various wildlife and animal meat for consumption in China.
 
From the research finding, a six-month evolutionary history of SARS-CoV-2 was witnessed by characterizing the total genome of 821 samples using comparative phylogenomic approaches.
 
The analyses produced striking inclusive results that may guide scientist for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively.
 
From the research the viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase.
 
Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R0 were estimated to be 47.43 per year, 5.39 days and 2.72, respectively.
 
Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain.
 
The researchers arrived at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, vi rulence and immune response.
 
Although Wuhan province of China has been reported as origin place of SARS-CoV-2, the phylogeny and network strongly suggested that the virus samples from Guangdong province forms the ancestral branches. Wuhan has been widely cited as origin place for the official first case report, and possibly biased phylogenetic reconstructions either due to absence of samples from Guangdong in the data sets or phylogenetic trees constrained by Wuhan as outgroup. The Guangdong province is known as the largest import and export centre in China, where SARS was also first emerged and caused a global epidemic in 2003.
 
Besides, not all reported early cases were Wuhan’s wet market related and a potential intermediate host Malayan pangolins were illegally traded in Southern China, particularly in Guangdong province . These evidences implicitly support the hypothesis that SARS-CoV-2 originated from Guangdong, not Wuhan. The emergence time of SARS-CoV-2 based on Bayesian inference was estimated as 10 September 2019 about three months earlier than the date of first reported case in December 2019.
 
Most significantly, although the SARS-CoV2 genomes have been evolving under nearly neutral or purifying selection, one codon for each of nsp3 and nsp6 encoding sequences were found to be positively selected. These positively selected codons may enhance the function of replicase proteins. The positively selected codon in nsp3 was reported for the first time and codes threonine in pangolin CoV and serine in BetaCoV England 1. Considering the multiple interactions of NAB with other nonstructural proteins such as nsp2, nsp5, orf3a as well as other domains of nsp3, this substitution seems to be significant due to altering both chemical and structural features of the involved protein. The nsp6 was located at the endoplasmic reticulum (ER) generating autophagosomes, has the positively selected substitution of leucine to phenylalanine and indicated a signal of structural change in the protein. This was also reported by Benvenuto et al. and it appears to be variable in other coronaviruses as valine, isoleucine and leucine . https://www.journalofinfection.com/article/S0163-4453(20)30186-9/fulltext
 
The results of the present study lead the researchers to the following foremost conclusions. Although, six months evolution of viral genome is nearly neutral, one codon for each of nsp3 and nsp6 encoding sequences were positively selected and should be closely monitored. The nsp3 and N, S and M genes have to be further investigated, the potential sides for vaccines or drug studies, as the substitution rate per these genes show departure from the overall rate.
 
It should be noted that declining trend in the R0, appears to be the outcome of preventive actions taken worldwide and must be maintained and is no way related to the possibility that the virus is weakening, rather on the contrary it is evolving more potently but in a “smart” manner.. “allowing it to find more host but to destroy the host slowly.”
 
The researchers advocate that more research is done to validate their findings and to keep strict surveillance on the evolutionary aspects of the SARS-Cov-2 coronavirus.
 
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