Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

Abstract

Background: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat-SARS-like coronavirus sequences. Specifically, in the 5'-part spanning the first 11,498 nucleotides and the last 3'-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat-SARS-like coronavirus sequences, whereas in the middle region spanning the 3'-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions: The levels of genetic similarity between the 2019-nCoV and RaTG13suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely.We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention. author/funder. All rights reserved. No reuse allowed without permission.

Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV

“…Additionally, Hibecovirus with Bat Hp-betacoronavirus/Zhe-jiang2013, as the representative species, was the most closely related subgenus of Betacoronavirus to Sarbecovirus as compared to other subgenera, including Merbecovirus (under which MERS-CoV has been classified), Nobecovirus, and Embecovirus. These findings agree with previous phylogenetic tree and similarity plot data (Paraskevis et al, 2020). 2019-nCoV was found to be more closely related to the batinfecting Sarbecovirus species, Bat SARS-like coronavirus, and BetaCoV RaTG13 than to the SARS coronavirus that infects humans.…”

“…Instead, it has been suggested that there is an animal mediator for virus transmission from bats to humans, similar to the previous cases of SARS-CoV and MERS-CoV, wherein the masked palm civet (Paguma larvata) and dromedary camel (Camelus dromedarius) act as intermediate hosts, respectively (Lu et al, 2020). Although coronaviruses can exchange genetic material during coinfection, a recent report described the lack of a mosaic relationship of 2019-nCoV to the closely related Sarbecovirus, indicating the lack of a recombination event in the emergence of 2019-nCoV (Paraskevis et al, 2020). Hence, 2019-nCoV likely emerged from the accumulation of mutations responding to altered selective pressures or from the infidelity of RNA polymerase perpetuated as replication-neutral mutations.…”

“…A previously reported comprehensive similarity plot revealed notable mutational hotspots and conserved regions of the genome nucleotide positions of 2019-nCoV against closely related coronaviruses (Lu et al, 2020;Paraskevis et al, 2020). The present findings provide a different perspective of the similarity among Orthocoronavirinae species, using a cluster tree developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins.…”

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China

“…coronaviruses, but a recent report has subsequently identified a bat CoVs sequence, RaTG13, with 92-96% sequence identity with the novel virus, demonstrating that RaTG13 is the closest relative of the SARS-CoV-2 and forms a distinct lineage from other SARS-CoVs. This rejects the hypothesis of emergence as a result of a recombination event [94,96]. Even though there are high similarities between SARS-CoV-2 S and RaTG13 S, there are two distinct differences: one is an "RRAR" furin recognition site formed by an insertion residues in the S1/S2 protease cleavage site in SARS-CoV-2, rather than the single Arginine in SARS-CoV [97][98][99][100][101]; the other difference is the presence of 29 variant residues between SARS-CoV-2 S and RaTG13 S, 17 of which mapped to the receptor binding domain (RBD) [97].…”

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

“…Previous reports showed that species from the bat genera Rhinolophus in southern China are a rich pool of SARS-like-CoVs, which belong to the subgenera Sarbecovirus. These viruses exhibit rich genetic diversity and frequent recombination events, which may increase the potential for cross-species transmission [7,42,[51][52][53][54][55]. Here, we reconstructed the evolutionary history of the 2019-nCoV cluster (Box Box 1.…”