Wuhan-1 was not the direct ancestor of all the early coronavirus infections globally



3/11/2023, 6:56:18 PM

In light of the current congressional Re investigation of the covid origins we thoughts it’s important to remind about The 2021 Oxford team work who used mutational order approach (MOA) to reconstruct the history of mutations concluded that Wuhan-1 was not the direct ancestor of all the early coronavirus infections globally that gave rise sarscov2 pandemic . The team applied MOA to 49 common single nucleotide variants (SNVs) in the 29KG data set and used the inferred mutation history to denote key groups of mutations by assigning Greek symbols (μ, ν, α, β, γ, δ, and ε) to them “

One of the most important missed information by the the congressional investigation so far is the EARLIER by mutational order approach sarscov2 v lineage circulated in North America but remained undetected due to absent testing prior to 2020. The earlier than wuhan-1 north american prosarscov2 v lineages circulation is important in light of discussed in 2014-2015 coronavirus polybasic cleavage site gain of function work and the consequential coronavirus vaccine patents obtained by the USgovernment from the NIAID. US Application 62/412,703 Filed on 2016-10-25 in 2016-2017 “Inventors at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases have developed a novel CoV S protein vaccine antigen. This technology employs protein engineering to stabilize S in its prefusion conformation, preventing structural rearrangement, and exposing antigenically preferable surfaces. “

Patent Cooperation Treaty PCT/US2017/058370 Filed on 2017-10-25

US Patent 10,960,070 Filed on 2019-04-24

“The genomes containing the ν lineage, sampled in North America, descended from an earlier ancestor that also gave rise to the genome (α lineage) !!! at the root of Pekar et al. (2021) phylogeny. Therefore, our analysis has revealed an earlier MRCA ( most recent common ancestor) than that detectable by considering a smaller subset of sequences from China.”…

IMPORTANT !!!>>> “The ν lineage, detected in the United States in February 2020, is an even earlier descendant of proCoV2 and is a sibling of the α lineage). These lineages may not have been detected earlier because of the lack of sequencing in 2019, and it is likely that some originated early and spread around the world, whereas others evolved from proCoV2 or its early descendant in different parts of the world. Again, thousands of these coronavirus genomes were found throughout the world (fig. 3, yellow box). None of these genomes contained the widely studied spike protein mutant (D614G), a β mutation that occurred in the genomes carrying all three α variants and was first seen in late January 2020. Therefore, the proCoV2 (MRCA) and a large diversity of its early descendants were all able to spread in the global human population.

“The Progenitor Genome and the Index Case

The root of the mutation tree is the most recent common ancestor (MRCA) of all the genomes analyzed, which gave rise to two early coronavirus lineages (ν and α; fig. 2). The MRCA genome was the progenitor of all SARS-CoV-2 infections globally, henceforth proCoV2, and was likely carried by the “first detectable” case of human transmission in the COVID-19 pandemic (index case). A comparison of proCoV2 with Wuhan-1 genomes revealed three differences in 49 positions analyzed, which was also true for other reference genomes (fig. 1c). This suggests that the Wuhan-1 (EPI_ISL 402123) and the other earliest sampled genomes are derived coronavirus strains that arose from proCoV2 after the divergence of ν and α lineages (fig. 2).

According to the mutational history, the Wuhan-1 strain evolved by three successive α mutations (two synonymous and one nonsynonymous) in proCoV2 (α1, α2, and α3). Importantly, three closely related nonhuman coronavirus genomes (bats and pangolin) all have the same base at these positions as does the proCoV2 genome, suggesting that the ancestral genome did not contain α variants.!!! Furthermore, genomes with ν variants of proCoV2 do not contain the other 47 variants, all of which occurred on the genomic background containing α1–α3.

!!!These facts support the inference that coronaviruses lacking α variants were the ancestors of Wuhan-1!!!!

and other genomes sampled in December 2019 in China (fig. 1c). Therefore, we conclude that Wuhan-1 was not the direct ancestor of all the early coronavirus infections globally”…

“The mutational history from proCoV2 to Wuhan-1 genome points to the presence of measurable coronavirus diversity before the earliest recognized coronavirus outbreak in December 2019 (fig. 1). The presence of such diversity has been acknowledged and analyzed, for example, Pekar et al. (2021), but variants present in this diverse population were not identified. Our analyses clearly show that the ancestors of the Wuhan-1 genome gave rise to a diversity of Wuhan-1’s sibling coronavirus lineages (α3a–α3j; figs. 1 and 3). These sibling coronavirus lineages were detected in China in January 2020 (α3b and α3f) and February 2020 in Asia (α3c–α3e) and Europe (α3a, α3g–α3j) (table 1). Thousands of genomes in the 29KG data set belong to siblings and ancestors of Wuhan-1 (table 1 and fig. 3, yellow box). However, the paucity of genomes sampled in 2019 makes it impossible to establish the date and location of origin precisely, but some must have originated before the first detection of the outbreak. !!!

Notably, the evolution of α3 was preceded by the evolution of α2 and α1 lineages, with α1 spawning multiple offshoots first detected in Europe in February 2020 (α1a–3)”

Quote from : An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic Author: Kumar, Sudhir; Tao, Qiqing Publication: Molecular Biology and Evolution Publisher: Oxford University Press Date: 2021-05-04 Copyright © 2021, Oxford University Press