Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes

Rogozin, Igor B.; Saura, Andreu; Bykova, Anastassia; Brover, Vyacheslav; Yurchenko, Vyacheslav

doi:10.3390/microorganisms11010229

Cited by 6 publications

(19 citation statements)

References 55 publications

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“…This puzzling observation echoes with an observed evolutionary trend in SARS-CoV-2 accessory proteins: it is well-known that there are many deletions in the ORF7a-ORFb-ORF8 complex in SARS-CoV-2 [ 33 – 38 ]. Our recent analysis of deletion in the SAR-CoV-2 genome suggested that the density of deletions (the number of deletions divided by the gene length) for ORF7a and ORF8 is always much higher than that for other SARS-CoV-2 genes [ 39 ]. Interestingly, a prominent feature of all the studied deletions is that they predominantly located around the middle of the SARS-CoV-2 genes resembling the situation with a 29-nt deletion in SAR-CoV ORF8 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a prominent feature of all the studied deletions is that they predominantly located around the middle of the SARS-CoV-2 genes resembling the situation with a 29-nt deletion in SAR-CoV ORF8 . It should be noted that a hypervariability in SARS-CoV-2 ORF7A and ORF8 is not associated with mechanisms of deletions [ 39 ]. Thus, these deletions are likely to reflect recurrent searches of functional “space” of accessory protein combinations to achieve their more advantageous configurations.…”

Section: Discussionmentioning

confidence: 99%

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The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection

et al. 2023

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Background Accessory proteins have diverse roles in coronavirus pathobiology. One of them in SARS-CoV (the causative agent of the severe acute respiratory syndrome outbreak in 2002–2003) is encoded by the open reading frame 8 (ORF8). Among the most dramatic genomic changes observed in SARS-CoV isolated from patients during the peak of the pandemic in 2003 was the acquisition of a characteristic 29-nucleotide deletion in ORF8. This deletion cause splitting of ORF8 into two smaller ORFs, namely ORF8a and ORF8b. Functional consequences of this event are not entirely clear. Results Here, we performed evolutionary analyses of ORF8a and ORF8b genes and documented that in both cases the frequency of synonymous mutations was greater than that of nonsynonymous ones. These results suggest that ORF8a and ORF8b are under purifying selection, thus proteins translated from these ORFs are likely to be functionally important. Comparisons with several other SARS-CoV genes revealed that another accessory gene, ORF7a, has a similar ratio of nonsynonymous to synonymous mutations suggesting that ORF8a, ORF8b, and ORF7a are under similar selection pressure. Conclusions Our results for SARS-CoV echo the known excess of deletions in the ORF7a-ORF7b-ORF8 complex of accessory genes in SARS-CoV-2. A high frequency of deletions in this gene complex might reflect recurrent searches in “functional space” of various accessory protein combinations that may eventually produce more advantageous configurations of accessory proteins similar to the fixed deletion in the SARS-CoV ORF8 gene.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection

et al. 2023

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“…The obvious pitfall of this approach is frequently missing recurrent mutations, reversals (backward mutations), and indels (insertions and deletions). However, the approach is useful for analyses of long insertions and deletions [28,30,31]. A substantially more sophisticated approach for the prediction of mutations is based on phylogenetic inferences [7] and allows detection of recurrent mutations and reversals.…”

Section: Reconstructions and Analyses Of Mutation Spectra: Methodolog...mentioning

confidence: 99%

“…Phylogenetic trees (i.e., Figure 2) can be inferred using various methods, yet all of them have certain limitations. As an example, the least squares distance and maximum parsimony approaches to predicting deletions in over 600 thousand SARS-CoV-2 genomes produced many false positive hits [30]. Inaccuracies of phylogenetic reconstructions and the difficulty of predicating the ancestral sequences that are used to infer mutations are well known [32,33].…”

Section: Reconstructions and Analyses Of Mutation Spectra: Methodolog...mentioning

confidence: 99%

“…SARS-CoV-2 has accumulated many mutations during the several years of the pandemic [36]. Mutations leading to amino acid substitutions constitute the primary raw material for genetic variation; however, many insertions, deletions, and recombination events are likely to be critical elements in the macro-and microevolution of coronavirus [30,46,47]. Understanding the molecular mechanisms of mutations is important in itself, but it is also essential for understanding the role of mutation hotspots and uncovering the pathways of their appearance.…”

Section: Molecular Mechanisms Of Mutationsmentioning

confidence: 99%

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Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2

Rogozin,

Saura,

Poliakov

et al. 2024

IJMS

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SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.

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Genomic surveillance and vaccine response to the dominant SARS-CoV-2 XBB lineage in Rio Grande do Sul

Piccoli,

y Castro,

Tessele

et al. 2024

Sci Rep

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The COVID-19 pandemic has been marked by novel viral variants, posing challenges to global public health. Recombination, a viral evolution mechanism, is implicated in SARS-CoV-2's ongoing evolution. The XBB recombinant lineage, known for evading antibody-mediated immunity, exhibits higher transmissibility without increased disease severity. We investigated the prevalence and genomic features of XBB in SARS-CoV-2-positive cases in Rio Grande do Sul (RS), Brazil. We sequenced 357 samples from epidemiological weeks (EW) 47/2022 to 17/2023, and included 389 publicly available sequences. Clinical and epidemiological data were obtained from DATASUS, e-SUS, and SIVEP GRIPE (data recording systems of the Brazilian Ministry of Health). Of these, 143 were classified as XBB and 586 were other Omicron lineages. In March 2023 (EW 10), XBB became dominant, accounting for 83.3% of cases. 97.7% of XBB-infected patients successfully recovered from the infection, with a low mortality rate (2.3%). Even after receiving three vaccine doses and having been previously infected, 59.5% of the patients experienced reinfection with XBB. However, for 54% of the individuals, the interval between their XBB infection and the last vaccine dose exceeded one year, potentially leading to a decline in antibody levels. In addition, we identified 90 mutations in RS circulating XBB, spread throughout the genome, notably in the Spike protein region associated with immune resistance. This study provides insights into the dynamics and impact of a recombinant variant becoming predominant for the first time in the state. Continued surveillance of SARS-CoV-2 genomic evolution is crucial for effective public health management.

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Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes

Cited by 6 publications

References 55 publications

The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection

The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection

Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2

Genomic surveillance and vaccine response to the dominant SARS-CoV-2 XBB lineage in Rio Grande do Sul

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