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

. 2023 Jan 16 ; 11 (1) : . [epub] 20230116

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article

Grant support
N/A Intramural Research Program of the National Library of Medicine at the National Institutes of Health
SGS/PřF/2023 Ministry of Education Youth and Sports

Links

PubMed 36677521
PubMed Central PMC9862619
DOI 10.3390/microorganisms11010229
PII: microorganisms11010229
Knihovny.cz E-resources

The analysis of deletions may reveal evolutionary trends and provide new insight into the surprising variability and rapidly spreading capability that SARS-CoV-2 has shown since its emergence. To understand the factors governing genomic stability, it is important to define the molecular mechanisms of deletions in the viral genome. In this work, we performed a statistical analysis of deletions. Specifically, we analyzed correlations between deletions in the SARS-CoV-2 genome and repetitive elements and documented a significant association of deletions with runs of identical (poly-) nucleotides and direct repeats. Our analyses of deletions in the accessory genes of SARS-CoV-2 suggested that there may be a hypervariability in ORF7A and ORF8 that is not associated with repetitive elements. Such recurrent search in a "sequence space" of accessory genes (that might be driven by natural selection) did not yet cause increased viability of the SARS-CoV-2 variants. However, deletions in the accessory genes may ultimately produce new variants that are more successful compared to the viral strains with the conventional architecture of the SARS-CoV-2 accessory genes.

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Lovett S.T. Encoded errors: Mutations and rearrangements mediated by misalignment at repetitive DNA sequences. Mol. Microbiol. 2004;52:1243–1253. doi: 10.1111/j.1365-2958.2004.04076.x. PubMed DOI

Bzymek M., Lovett S.T. Instability of repetitive DNA sequences: The role of replication in multiple mechanisms. Proc. Natl. Acad. Sci. USA. 2001;98:8319–8325. doi: 10.1073/pnas.111008398. PubMed DOI PMC

Bzymek M., Saveson C.J., Feschenko V.V., Lovett S.T. Slipped Misalignment Mechanisms of Deletion Formation: In Vivo Susceptibility to Nucleases. J. Bacteriol. 1999;181:477–482. doi: 10.1128/JB.181.2.477-482.1999. PubMed DOI PMC

Bi X., Liu L.F. recA-independent and recA-dependent Intramolecular Plasmid Recombination: Differential Homology Requirement and Distance Effect. J. Mol. Biol. 1994;235:414–423. doi: 10.1006/jmbi.1994.1002. PubMed DOI

Chou Q. Minimizing deletion mutagenesis artifact during Taq DNA polymerase PCR by E. coli SSB. Nucleic Acids Res. 1992;20:4371. doi: 10.1093/nar/20.16.4371. PubMed DOI PMC

Chédin F., Dervyn E., Dervyn R., Ehrlich S.D., Noirot P. Frequency of deletion formation decreases exponentially with distance between short direct repeats. Mol. Microbiol. 1994;12:561–569. doi: 10.1111/j.1365-2958.1994.tb01042.x. PubMed DOI

Lovett S., Gluckman T.J., Simon P.J., Sutera V.A., Drapkin P.T. Recombination between repeats in Escherichia coli by a recA-independent, proximity-sensitive mechanism. Mol. Gen. Genet. 1994;245:294–300. doi: 10.1007/BF00290109. PubMed DOI

Dianov G.L., Kuzminov A.V., Mazin A.V., Salganik R.I. Molecular mechanisms of deletion formation in Escherichia coli plasmids. I. Deletion formation mediated by long direct repeats. Mol. Gen. Genet. 1991;228:153–159. doi: 10.1007/BF00282460. PubMed DOI

Mazin A.V., Kuzminov A.V., Dianov G.L., Salganik R.I. Mechanisms of deletion formation in Escherichin coli plasmids. II. Deletions mediated by short direct repeats. Mol. Gen. Genet. 1991;228:209–214. doi: 10.1007/BF00282467. PubMed DOI

Albertini A.M., Hofer M., Calos M.P., Miller J.H. On the formation of spontaneous deletions: The importance of short sequence homologies in the generation of large deletions. Cell. 1982;29:319–328. doi: 10.1016/0092-8674(82)90148-9. PubMed DOI

Efstratiadis A., Posakony J.W., Maniatis T., Lawn R.M., O’Connell C., Spritz R.A., Deriel J.K., Forget B.G., Weissman S.M., Slightom J.L., et al. The structure and evolution of the human β-globin gene family. Cell. 1980;21:653–668. doi: 10.1016/0092-8674(80)90429-8. PubMed DOI

Streisinger G., Okada Y., Emrich J., Newton J., Tsugita A., Terzaghi E., Inouye M. Frameshift Mutations and the Genetic Code. Cold Spring Harb. Symp. Quant. Biol. 1966;31:77–84. doi: 10.1101/SQB.1966.031.01.014. PubMed DOI

Lovett S.T., Feschenko V.V. Stabilization of diverged tandem repeats by mismatch repair: Evidence for deletion formation via a misaligned replication intermediate. Proc. Natl. Acad. Sci. USA. 1996;93:7120–7124. doi: 10.1073/pnas.93.14.7120. PubMed DOI PMC

Trinh T.Q., Sinden R.R. Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature. 1991;352:544–547. doi: 10.1038/352544a0. PubMed DOI

Bierne H., Vilette D., Ehrlich S.D., Michel B. Isolation of a dnaE mutation which enhances RecA-independent homologous recombination in the Escherichia coli chromosome. Mol. Microbiol. 1997;24:1225–1234. doi: 10.1046/j.1365-2958.1997.4381795.x. PubMed DOI

Saveson C.J., Lovett S.T. Enhanced Deletion Formation by Aberrant DNA Replication in Escherichia coli. Genetics. 1997;146:457–470. doi: 10.1093/genetics/146.2.457. PubMed DOI PMC

Hu X., Worton R.G. Partial gene duplication as a cause of human disease. Hum. Mutat. 1992;1:3–12. doi: 10.1002/humu.1380010103. PubMed DOI

Krawczak M., Cooper D.N. Gene deletions causing human genetic disease: Mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum. Genet. 1991;86:425–441. doi: 10.1007/BF00194629. PubMed DOI

Kondrashov A.S., Rogozin I.B. Context of deletions and insertions in human coding sequences. Hum. Mutat. 2004;23:177–185. doi: 10.1002/humu.10312. PubMed DOI

Warren S.T. The Expanding World of Trinucleotide Repeats. Science. 1996;271:1374–1375. doi: 10.1126/science.271.5254.1374. PubMed DOI

Wu A., Wang L., Zhou H.-Y., Ji C.-Y., Xia S.Z., Cao Y., Meng J., Ding X., Gold S., Jiang T., et al. One year of SARS-CoV-2 evolution. Cell Host Microbe. 2021;29:503–507. doi: 10.1016/j.chom.2021.02.017. PubMed DOI PMC

Garushyants S.K., Rogozin I.B., Koonin E.V. Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring. Commun. Biol. 2021;4:1343. doi: 10.1038/s42003-021-02858-9. PubMed DOI PMC

Zinzula L. Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2. Biochem. Biophys. Res. Commun. 2021;538:116–124. doi: 10.1016/j.bbrc.2020.10.045. PubMed DOI PMC

Peacock T.P., Penrice-Randal R., Hiscox J.A., Barclay W.S. SARS-CoV-2 one year on: Evidence for ongoing viral adaptation. J. Gen. Virol. 2021;102:001584. doi: 10.1099/jgv.0.001584. PubMed DOI PMC

Ceraolo C., Giorgi F.M. Genomic variance of the 2019-nCoV coronavirus. J. Med. Virol. 2020;92:522–528. doi: 10.1002/jmv.25700. PubMed DOI PMC

Michel C.J., Mayer C., Poch O., Thompson J.D. Characterization of accessory genes in coronavirus genomes. Virol. J. 2020;17:131. doi: 10.1186/s12985-020-01402-1. PubMed DOI PMC

Panzera Y., Calleros L., Goñi N., Marandino A., Techera C., Grecco S., Ramos N., Frabasile S., Tomás G., Condon E., et al. Consecutive deletions in a unique Uruguayan SARS-CoV-2 lineage evidence the genetic variability potential of accessory genes. PLoS ONE. 2022;17:e0263563. doi: 10.1371/journal.pone.0263563. PubMed DOI PMC

Grubaugh N.D., Petrone M.E., Holmes E.C. We shouldn’t worry when a virus mutates during disease outbreaks. Nat. Microbiol. 2020;5:529–530. doi: 10.1038/s41564-020-0690-4. PubMed DOI PMC

McCarthy K.R., Rennick L.J., Nambulli S., Robinson-McCarthy L.R., Bain W.G., Haidar G., Duprex W.P. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science. 2021;371:1139–1142. doi: 10.1126/science.abf6950. PubMed DOI PMC

Narayanan K., Huang C., Makino S. SARS coronavirus accessory proteins. Virus Res. 2008;133:113–121. doi: 10.1016/j.virusres.2007.10.009. PubMed DOI PMC

Muth D., Corman V.M., Roth H., Binger T., Dijkman R., Gottula L.T., Gloza-Rausch F., Balboni A., Battilani M., Rihtarič D., et al. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Sci. Rep. 2018;8:15177. doi: 10.1038/s41598-018-33487-8. PubMed DOI PMC

Addetia A., Xie H., Roychoudhury P., Shrestha L., Loprieno M., Huang M.-L., Jerome K.R., Greninger A.L. Identification of multiple large deletions in ORF7a resulting in in-frame gene fusions in clinical SARS-CoV-2 isolates. J. Clin. Virol. 2020;129:104523. doi: 10.1016/j.jcv.2020.104523. PubMed DOI PMC

Panzera Y., Ramos N., Frabasile S., Calleros L., Marandino A., Tomás G., Techera C., Grecco S., Fuques E., Goñi N., et al. A deletion in SARS-CoV-2 ORF7 identified in COVID-19 outbreak in Uruguay. Transbound. Emerg. Dis. 2021;68:3075–3082. doi: 10.1111/tbed.14002. PubMed DOI PMC

Alisoltani A., Jaroszewski L., Iyer M., Iranzadeh A., Godzik A. Increased Frequency of Indels in Hypervariable Regions of SARS-CoV-2 Proteins—A Possible Signature of Adaptive Selection. Front. Genet. 2022;13:875406. doi: 10.3389/fgene.2022.875406. PubMed DOI PMC

Pancer K., Milewska A., Owczarek K., Dabrowska A., Kowalski M., Łabaj P.P., Branicki W., Sanak M., Pyrc K. The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans. PLOS Pathog. 2020;16:e1008959. doi: 10.1371/journal.ppat.1008959. PubMed DOI PMC

Poliakov E., Koonin E.V., Rogozin I.B. Impairment of translation of in neurons as a putative causative factor for autism. Biol. Direct. 2014;10:16. doi: 10.1186/1745-6150-9-16. PubMed DOI PMC

Khromov-Borisov N.N., Rogozin I., Henriques J.A.P., de Serres F.J. Similarity pattern analysis in mutational distributions. Mutat. Res. 1999;430:55–74. doi: 10.1016/S0027-5107(99)00148-7. PubMed DOI

Rogozin I.B., Babenko V.N., Milanesi L., Pavlov Y.I. Computational analysis of mutation spectra. Briefings Bioinform. 2003;4:210–227. doi: 10.1093/bib/4.3.210. PubMed DOI

Li J.-Y., Liao C.-H., Wang Q., Tan Y.-J., Luo R., Qiu Y., Ge X.-Y. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Res. 2020;286:198074. doi: 10.1016/j.virusres.2020.198074. PubMed DOI PMC

Stadler K., Masignani V., Eickmann M., Becker S., Abrignani S., Klenk H.-D., Rappuoli R. SARS—Beginning to understand a new virus. Nat. Rev. Microbiol. 2003;1:209–218. doi: 10.1038/nrmicro775. PubMed DOI PMC

Mohammed M.E.A. The percentages of SARS-CoV-2 protein similarity and identity with SARS-CoV and BatCoV RaTG13 proteins can be used as indicators of virus origin. J. Proteins Proteom. 2021;12:81–91. doi: 10.1007/s42485-021-00060-3. PubMed DOI PMC

Nelson C.A., Pekosz A., Lee C.A., Diamond M.S., Fremont D.H. Structure and Intracellular Targeting of the SARS-Coronavirus Orf7a Accessory Protein. Structure. 2005;13:75–85. doi: 10.1016/j.str.2004.10.010. PubMed DOI PMC

Tan Y., Schneider T., Leong M., Aravind L., Zhang D. Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses. mBio. 2020;11:e00760-20. doi: 10.1128/mBio.00760-20. PubMed DOI PMC

Lau S.K.P., Feng Y., Chen H., Luk H.K.H., Yang W.-H., Li K.S.M., Zhang Y.-Z., Huang Y., Song Z.-Z., Chow F.W.-N., et al. Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination. J. Virol. 2015;89:10532–10547. doi: 10.1128/JVI.01048-15. PubMed DOI PMC

Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-CoV-2. Nat. Med. 2020;26:450–452. doi: 10.1038/s41591-020-0820-9. PubMed DOI PMC

Rasmussen A.L. On the origins of SARS-CoV-2. Nat. Med. 2021;27:9. doi: 10.1038/s41591-020-01205-5. PubMed DOI

Postnikova O.A., Uppal S., Huang W., Kane M.A., Villasmil R., Rogozin I.B., Poliakov E., Redmond T.M. The Functional Consequences of the Novel Ribosomal Pausing Site in SARS-CoV-2 Spike Glycoprotein RNA. Int. J. Mol. Sci. 2021;22:6490. doi: 10.3390/ijms22126490. PubMed DOI PMC

Seyran M., Pizzol D., Adadi P., El-Aziz T.M.A., Hassan S.S., Soares A., Kandimalla R., Lundstrom K., Tambuwala M., Aljabali A.A.A., et al. Questions concerning the proximal origin of SARS-CoV-2. J. Med. Virol. 2020;93:1204–1206. doi: 10.1002/jmv.26478. PubMed DOI PMC

Oostra M., de Haan C.A.M., Rottier P.J.M. The 29-Nucleotide Deletion Present in Human but Not in Animal Severe Acute Respiratory Syndrome Coronaviruses Disrupts the Functional Expression of Open Reading Frame 8. J. Virol. 2007;81:13876–13888. doi: 10.1128/JVI.01631-07. PubMed DOI PMC

Liu D.X., Fung T.S., Chong K.K.-L., Shukla A., Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Antivir. Res. 2014;109:97–109. doi: 10.1016/j.antiviral.2014.06.013. PubMed DOI PMC

Guan Y., Zheng B.J., He Y.Q., Liu X.L., Zhuang Z.X., Cheung C.L., Luo S.W., Li P.H., Zhang L.J., Guan Y.J., et al. Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China. Science. 2003;302:276–278. doi: 10.1126/science.1087139. PubMed DOI

The Chinese SARS Molecular Epidemiology Consortium Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China. Science. 2004;303:1666–1669. doi: 10.1126/science.1092002. PubMed DOI

Mohammad S., Bouchama A., Mohammad Alharbi B., Rashid M., Saleem Khatlani T., Gaber N.S., Malik S.S. SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence. Pathogens. 2020;9:677. doi: 10.3390/pathogens9090677. PubMed DOI PMC

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