The Mutational Landscape of SARS-CoV-2

Mutation research is crucial for detecting and treating SARS-CoV-2 and developing vaccines. Using over 5,300,000 sequences from SARS-CoV-2 genomes and custom Python programs, we analyzed the mutational landscape of SARS-CoV-2. Although almost every nucleotide in the SARS-CoV-2 genome has mutated at some time, the substantial differences in the frequency and regularity of mutations warrant further examination. C>U mutations are the most common. They are found in the largest number of variants, pangolin lineages, and countries, which indicates that they are a driving force behind the evolution of SARS-CoV-2. Not all SARS-CoV-2 genes have mutated in the same way. Fewer non-synonymous single nucleotide variations are found in genes that encode proteins with a critical role in virus replication than in genes with ancillary roles. Some genes, such as spike (S) and nucleocapsid (N), show more non-synonymous mutations than others. Although the prevalence of mutations in the target regions of COVID-19 diagnostic RT-qPCR tests is generally low, in some cases, such as for some primers that bind to the N gene, it is significant. Therefore, ongoing monitoring of SARS-CoV-2 mutations is crucial. The SARS-CoV-2 Mutation Portal provides access to a database of SARS-CoV-2 mutations.

[1]  F. Carletti,et al.  Detection of SARS-CoV-2 Variants via Different Diagnostics Assays Based on Single-Nucleotide Polymorphism Analysis , 2023, Diagnostics.

[2]  S. Hassan,et al.  A conserved oligomerization domain in the disordered linker of coronavirus nucleocapsid proteins , 2023, Science advances.

[3]  T. Akaishi,et al.  Insertion and deletion mutations preserved in SARS-CoV-2 variants , 2023, Archives of Microbiology.

[4]  Jingyun Yang,et al.  Research progress in spike mutations of SARS‐CoV‐2 variants and vaccine development , 2023, Medicinal research reviews.

[5]  Jordan J. Clark,et al.  The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection , 2023, Genome Biology.

[6]  L. Cendron,et al.  SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works , 2023, International journal of molecular sciences.

[7]  M. Abbasian,et al.  Global landscape of SARS-CoV-2 mutations and conserved regions , 2023, Journal of Translational Medicine.

[8]  Baoyi Liu,et al.  Evidence Supporting That C-to-U RNA Editing Is the Major Force That Drives SARS-CoV-2 Evolution , 2023, Journal of Molecular Evolution.

[9]  D. Motooka,et al.  Impact of G29179T mutation on two commercial PCR assays for SARS-CoV-2 detection , 2023, Journal of Virological Methods.

[10]  Marc C. Johnson,et al.  Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge , 2023, International journal of molecular sciences.

[11]  H. Ode,et al.  Cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome , 2023, Nucleic acids research.

[12]  A. Venkatakrishnan,et al.  Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants , 2023, Scientific Reports.

[13]  F. Betsou,et al.  New RT-PCR Assay for the Detection of Current and Future SARS-CoV-2 Variants , 2023, Viruses.

[14]  I. Rogozin,et al.  Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes , 2023, Microorganisms.

[15]  Adrià Cereto-Massagué,et al.  Prediction of Recurrent Mutations in SARS-CoV-2 Using Artificial Neural Networks , 2022, International journal of molecular sciences.

[16]  Bin Yin,et al.  C-to-U RNA deamination is the driving force accelerating SARS-CoV-2 evolution , 2022, Life Science Alliance.

[17]  Carla A. Cummins,et al.  Identification of mutations in SARS-CoV-2 PCR primer regions , 2022, Scientific Reports.

[18]  A. Swaminathan,et al.  SARS-CoV-2 Variants of Concern and Variations within Their Genome Architecture: Does Nucleotide Distribution and Mutation Rate Alter the Functionality and Evolution of the Virus? , 2022, Viruses.

[19]  G. Pujadas,et al.  Could nucleocapsid be a next-generation COVID-19 vaccine candidate? , 2022, International Journal of Infectious Diseases.

[20]  S. Tao,et al.  Natural selection pressure exerted on “Silent” mutations during the evolution of SARS-CoV-2: Evidence from codon usage and RNA structure , 2022, Virus Research.

[21]  P. Feng,et al.  The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness , 2022, Scientific Reports.

[22]  E. Giombini,et al.  SARS-CoV-2 Variants Identification: Overview of Molecular Existing Methods , 2022, Pathogens.

[23]  T. Reid,et al.  Nucleocapsid as a next-generation COVID-19 vaccine candidate , 2022, International Journal of Infectious Diseases.

[24]  J. Simpson,et al.  Emergence of a mutation in the nucleocapsid gene of SARS-CoV-2 interferes with PCR detection in Canada , 2022, Scientific Reports.

[25]  E. Domingo,et al.  SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations , 2022, Pathogens.

[26]  Jie Zhou,et al.  Rampant C-to-U deamination accounts for the intrinsically high mutation rate in SARS-CoV-2 spike gene , 2022, RNA.

[27]  Jiji Chen,et al.  Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein. , 2022, PNAS nexus.

[28]  P. Feng,et al.  The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness , 2022, bioRxiv.

[29]  Aiping Wu,et al.  Conserved Pattern and Potential Role of Recurrent Deletions in SARS-CoV-2 Evolution , 2022, Microbiology spectrum.

[30]  D. Castelo-Branco,et al.  The spike glycoprotein of SARS-CoV-2: A review of how mutations of spike glycoproteins have driven the emergence of variants with high transmissibility and immune escape , 2022, International Journal of Biological Macromolecules.

[31]  Q. Ye,et al.  The emergence and epidemic characteristics of the highly mutated SARS‐CoV‐2 Omicron variant , 2022, Journal of medical virology.

[32]  Gustaf E. Rydell,et al.  Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2 , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Gao,et al.  The emergence, genomic diversity and global spread of SARS-CoV-2 , 2021, Nature.

[34]  S. Maurer-Stroh,et al.  GISAID’s Role in Pandemic Response , 2021, China CDC weekly.

[35]  E. Callaway Beyond Omicron: what’s next for COVID’s viral evolution , 2021, Nature.

[36]  S. Kannan,et al.  Omicron (B.1.1.529) - variant of concern - molecular profile and epidemiology: a mini review. , 2021, European review for medical and pharmacological sciences.

[37]  E. Koonin,et al.  Template switching and duplications in SARS-CoV-2 genomes give rise to insertion variants that merit monitoring , 2021, Communications Biology.

[38]  R. Shafer,et al.  SARS-CoV-2 Variants and Their Relevant Mutational Profiles: Update Summer 2021 , 2021, Microbiology spectrum.

[39]  D. Speers,et al.  Single-Point Mutations in the N Gene of SARS-CoV-2 Adversely Impact Detection by a Commercial Dual Target Diagnostic Assay , 2021, Microbiology spectrum.

[40]  Chih-Kai Chang,et al.  SARS-CoV-2 variants with T135I nucleocapsid mutations may affect antigen test performance , 2021, International Journal of Infectious Diseases.

[41]  P. Auvinen,et al.  SARS‐CoV‐2 variant with mutations in N gene affecting detection by widely used PCR primers , 2021, Journal of medical virology.

[42]  Wei Hu,et al.  Structure-Based Primer Design Minimizes the Risk of PCR Failure Caused by SARS-CoV-2 Mutations , 2021, Frontiers in Cellular and Infection Microbiology.

[43]  Philip L. Tzou,et al.  The biological and clinical significance of emerging SARS-CoV-2 variants , 2021, Nature Reviews Genetics.

[44]  G. Dirani,et al.  A deletion in the N gene may cause diagnostic escape in SARS-CoV-2 samples , 2021, Diagnostic Microbiology and Infectious Disease.

[45]  C. Chakraborty,et al.  Evolution, Mode of Transmission, and Mutational Landscape of Newly Emerging SARS-CoV-2 Variants , 2021, mBio.

[46]  Mustafizur Rahman,et al.  Identification of Novel Mutations in the N Gene of SARS-CoV-2 That Adversely Affect the Detection of the Virus by Reverse Transcription-Quantitative PCR , 2021, Microbiology spectrum.

[47]  A. Godzik,et al.  The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins , 2021, PLoS Comput. Biol..

[48]  K. Zwirglmaier,et al.  In vitro evaluation of the effect of mutations in primer binding sites on detection of SARS-CoV-2 by RT-qPCR , 2021, bioRxiv.

[49]  P. Simmonds,et al.  Extensive C->U transition biases in the genomes of a wide range of mammalian RNA viruses; potential associations with transcriptional mutations, damage- or host-mediated editing of viral RNA , 2021, PLoS pathogens.

[50]  William T. Harvey,et al.  SARS-CoV-2 variants, spike mutations and immune escape , 2021, Nature Reviews Microbiology.

[51]  Irwin Jungreis,et al.  SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes , 2021, Nature Communications.

[52]  Nuno R. Faria,et al.  Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2 , 2021, PLoS biology.

[53]  Conor R. Walker,et al.  Mutation Rates and Selection on Synonymous Mutations in SARS-CoV-2 , 2021, Genome biology and evolution.

[54]  P. Sfikakis,et al.  The role of A-to-I RNA editing in infections by RNA viruses: Possible implications for SARS-CoV-2 infection , 2021, Clinical Immunology.

[55]  W. P. Duprex,et al.  Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape , 2021, Science.

[56]  Conor R. Walker,et al.  MUTATION RATES AND SELECTION ON SYNONYMOUS MUTATIONS IN SARS-COV-2 , 2021, bioRxiv.

[57]  P. Simmonds,et al.  Potential APOBEC-mediated RNA editing of the genomes of SARS-CoV-2 and other coronaviruses and its impact on their longer term evolution , 2021, Virology.

[58]  E. Hodcroft,et al.  Genetic Variants of SARS-CoV-2-What Do They Mean? , 2021, JAMA.

[59]  Haiyong Peng,et al.  SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity , 2020, Nature Communications.

[60]  J. Liao,et al.  Analysis of genomic distributions of SARS-CoV-2 reveals a dominant strain type with strong allelic associations , 2020, Proceedings of the National Academy of Sciences.

[61]  James T. Webber,et al.  Identification of a Polymorphism in the N Gene of SARS-CoV-2 That Adversely Impacts Detection by Reverse Transcription-PCR , 2020, Journal of Clinical Microbiology.

[62]  K. Korn,et al.  SARS-CoV-2 samples may escape detection because of a single point mutation in the N gene , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[63]  G. Wei,et al.  Host Immune Response Driving SARS-CoV-2 Evolution , 2020, Viruses.

[64]  Vineet D. Menachery,et al.  Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility , 2020, Nature.

[65]  Sebastian Maurer-Stroh,et al.  Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study , 2020, The Lancet.

[66]  Edward C. Holmes,et al.  A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology , 2020, Nature Microbiology.

[67]  D. Ramazzotti,et al.  Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity , 2020, bioRxiv.

[68]  S. Rowland-Jones,et al.  Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus , 2020, Cell.

[69]  P. Simmonds,et al.  Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories , 2020, mSphere.

[70]  M. Torcia,et al.  Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2 , 2020, Science Advances.

[71]  G. Wei,et al.  Mutations on COVID-19 diagnostic targets , 2020, Genomics.

[72]  F. Giorgi,et al.  Geographic and Genomic Distribution of SARS-CoV-2 Mutations , 2020, Frontiers in Microbiology.

[73]  G. Wei,et al.  Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine , 2020, J. Chem. Inf. Model..

[74]  M. Torcia,et al.  Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2 , 2020, bioRxiv.

[75]  Victor M Corman,et al.  Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[76]  E. Levanon,et al.  A-to-I RNA editing — immune protector and transcriptome diversifier , 2018, Nature Reviews Genetics.

[77]  J. Dudley,et al.  APOBECs and virus restriction. , 2015, Virology.

[78]  OUP accepted manuscript , 2022, Nucleic Acids Research.