Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic

Velazquez‐Salinas, Lauro; Zárate, Selene; Eberl, Samantha; Dp, Gladue; Novella, Isabel S.; Mv, Borca

doi:10.1101/2020.04.10.035964

Cited by 24 publications

(22 citation statements)

References 32 publications

(28 reference statements)

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“…The presence of multiple variants within China indicates early divergence events in early phase of the pandemic. Similar type of observations was also reported in a recent work on SARS-CoV-2 genomes (Velazquez-Salinas et al, 2020).…”

Section: Phylogenomic Study Of Sars-cov-2 Reveals the Appearance Of Dsupporting

confidence: 90%

Emergence of multiple variants of SARS-CoV-2 with signature structural changes

Bhowmik

Pal

Lahiri

et al. 2020

Preprint

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This study explores the divergence pattern of SARS-CoV-2 using whole genome sequences of the isolates from various COVID-19 affected countries. The phylogenomic analysis indicates the presence of at least four distinct groups of the SARS-CoV-2 genomes. The emergent groups have been found to be associated with signature structural changes in specific proteins. Also, this study reveals the differential levels of divergence patterns for the protein coding regions. Moreover, we have predicted the impact of structural changes on a couple of important viral proteins via structural modelling techniques. This study further advocates for more viral genetic studies with associated clinical outcomes and hosts' response for better understanding of SARS-CoV-2 pathogenesis enabling better mitigation of this pandemic situation.

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Section: Phylogenomic Study Of Sars-cov-2 Reveals the Appearance Of Dsupporting

confidence: 90%

Emergence of multiple variants of SARS-CoV-2 with signature structural changes

Bhowmik

Pal

Lahiri

et al. 2020

Preprint

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“…For example, artefactual biases in mutational processes could confound signatures of mutational hotspots [28][29][30][31][32][33] . The issue of whether or not recombination has occurred during the outbreak is critical to the immunological battle against the virus and is under intense debate [6,[34][35][36][37][38][39][40] . Because many tests of recombination assume that all mutations can only occur once at each site, recurrent mutation and systematic errors can confound signatures of recombination [6,26,35] .…”

Section: Figure 1: Effect Of Recurrent Sequencing Mutations On Phylogmentioning

confidence: 99%

Stability of SARS-CoV-2 Phylogenies

Turakhia

Thornlow

Gozashti

et al. 2020

Preprint

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The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade-and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse.Foreword:

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“…Therefore, a question arises as to whether ORF8 has descended directly from bat or pangolin coronavirus sources or some genome modification events have contributed towards its evolution. The coronavirus ORF8 region, along with nsp3, ORF3 and S, are considered to be among the rapidly evolving regions being flanked by recombination-prone sequences [36,62,67], thus augmenting the possible contribution of recombination in coronavirus and coronavirus element evolution. A recent publication has also reported the presence of recombination breakpoints around ORF8, raising the possibility of modular recombination occurring at both ends of ORF8 that are characterized by near identical nucleic acid sequences among SARS-CoVs and some bat CoVs [76].…”

Section: Sars-cov-2 Orf8 Evolutionary Pathwaymentioning

confidence: 99%

“…ORF8 is an accessory protein that is not shared by all members of subgenus sarbecovirus and it was the presence and location of ORF8 in the SARS-CoV-2 genome that led to the classification of SARS-CoV-2 genome with that of SARS-CoV [1]. SARS-CoV-2 Clade S subtype characteristics include the marker variant based on the T28144C mutation leading to L84S change in the ORF8 protein sequence [35], a positive selection that has resulted in the divergence of a separate phylogenetic group [36]. These accessory proteins offer functional flexibility to coronaviruses and accordingly are subject to alterations depending upon the condition in which they are expressed during the viral life cycle.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

et al. 2020

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The COVID-19 pandemic, in the first seven months, has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19, has proved to be a great challenge for its ability to spread in asymptomatic stages and the diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude, not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged, consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here, we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8 and predict its protein features. We have further reviewed current available literature regarding its function and comparatively evaluated these and other features of ORF8 and ORF8ab, its homolog from SARS-CoV. Because coronaviruses have been infecting humans repeatedly and might continue to do so, we therefore expect this study to aid in the development of holistic understanding of these proteins. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

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Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic

Cited by 24 publications

References 32 publications

Emergence of multiple variants of SARS-CoV-2 with signature structural changes

Emergence of multiple variants of SARS-CoV-2 with signature structural changes

Stability of SARS-CoV-2 Phylogenies

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

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