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Single Nucleotide Polymorphisms-SNPs01:05

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
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Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
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Highly Recurrent Multinucleotide Mutations in SARS-CoV-2.

Nicola De Maio1, Olivier Anoufa1,2, Kyle Smith3

  • 1European Molecular Biology Laboratory-European Bioinformatics Institute, EMBL-EBI, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.

Molecular Biology and Evolution
|October 24, 2025
PubMed
Summary
This summary is machine-generated.

Certain multinucleotide mutations in SARS-CoV-2 are surprisingly common, not random. Most are linked to transcription regulation, suggesting a template-switching mechanism during viral replication.

Keywords:
SARS-CoV-2complex mutationsmultinucleotide mutationspandemic-scale phylogeneticsrecurrent mutations

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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Area of Science:

  • Genomics
  • Virology
  • Evolutionary Biology

Background:

  • Multinucleotide mutations, altering multiple DNA bases simultaneously, are crucial in evolution and disease.
  • They are typically considered rare and random genetic events.
  • Understanding their patterns is vital for accurate genome analysis and disease research.

Purpose of the Study:

  • To investigate the frequency and patterns of multinucleotide mutations in SARS-CoV-2 genomes.
  • To identify potential mechanisms driving recurrent multinucleotide mutations.
  • To assess the impact of these mutations on genomic data analysis, particularly in evolutionary studies.

Main Methods:

  • Analysis of over 2 million publicly available SARS-CoV-2 genomes.
  • Identification and characterization of recurrent multinucleotide mutation patterns.
  • Correlation analysis between mutation sites and known genomic features, such as transcription regulatory sequences.
  • Evaluation of the impact on computational evolutionary biology tools, specifically recombination inference.

Main Results:

  • Discovery of highly recurrent multinucleotide mutations in SARS-CoV-2, occurring hundreds of times independently across lineages.
  • Identification that 97.6% of these recurrent mutations are associated with transcription regulatory sequences.
  • Proposal of a template-switching mechanism during viral transcription as a likely cause.
  • Demonstration that recurrent multinucleotide mutations contribute to approximately 12% of false positives in SARS-CoV-2 recombination inference.

Conclusions:

  • Recurrent multinucleotide mutations are a significant, non-random feature of SARS-CoV-2 evolution.
  • Transcription-associated template switching offers a plausible explanation for these observed mutation patterns.
  • These findings necessitate adjustments in computational methods for analyzing viral evolution and can improve the accuracy of genomic data interpretation.