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Related Concept Videos

Viral Mutations00:36

Viral Mutations

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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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The human body harbors a vast and diverse viral community known as the human virome. The virome includes bacteriophages that infect bacteria, and eukaryotic viruses that infect human cells. Transient dietary and environmental viruses also contribute to this dynamic ecosystem. Estimates suggest the human body may contain on the order of 10¹³ viral particles, though abundance varies widely by body site and detection method.Comprehensive characterization of the virome has become possible...
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Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
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Microbial genome evolution is a highly dynamic process shaped by continual gene gain and loss across species and strains. This genomic flexibility allows microorganisms to adapt rapidly to environmental pressures and interactions with other organisms. Central to understanding this diversity is the distinction between the core and pan genomes.The core genome comprises the genes shared by all sampled strains of a species, representing essential functions needed for fundamental cellular processes.
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Archaeal viruses play a crucial role in the ecosystems of extremophilic archaea, particularly those belonging to the phyla Euryarchaeota and Crenarchaeota. By shaping host evolution and facilitating gene transfer, these viruses influence microbial communities and contribute to genetic diversity in extreme environments. The archaea they infect thrive in acidic hot springs and hydrothermal vents characterized by high temperatures and low pH. Archaeal viruses exhibit remarkable structural...
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Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
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Human norovirus hyper-mutation revealed by ultra-deep sequencing.

José M Cuevas1, Marine Combe1, Manoli Torres-Puente2

  • 1Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|April 21, 2016
PubMed
Summary

Human noroviruses (NoVs) exhibit high mutation rates, contributing to rapid evolution and immune escape. This study quantifies spontaneous mutations, revealing a significant role for hypermutation, likely mediated by ADAR, in NoV diversity.

Keywords:
Hyper-mutationNext-generation sequencingNorovirusRNA virus

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Human noroviruses (NoVs) are a leading cause of gastroenteritis globally.
  • High mutation rates are hypothesized to drive rapid evolution and immune escape in RNA viruses like NoVs.
  • The precise rate and mutational spectrum of human NoVs remain unquantified.

Purpose of the Study:

  • To quantify the rate and spectrum of spontaneous mutations in human noroviruses.
  • To investigate the contribution of hypermutation to NoV genetic diversity.
  • To explore the potential role of ADAR-mediated editing in NoV mutagenesis.

Main Methods:

  • Analysis of intra-patient NoV capsid diversity using RT-PCR and ultra-deep sequencing (100,000x coverage) of 16 patient stool samples.
  • Transfection assays to assess mutation production within a single cell infection cycle.
  • Sequence analysis to identify mutation types, frequencies, and sequence contexts.

Main Results:

  • Ultra-deep sequencing revealed low-frequency variants with numerous U-to-C and A-to-G base transitions.
  • Transfection assays confirmed the presence of multiple U-to-C/A-to-G transitions, indicating hypermutation.
  • The observed mutation patterns and sequence contexts are consistent with ADAR-mediated RNA editing.

Conclusions:

  • Hypermutation significantly contributes to the spontaneous mutation rate of human noroviruses.
  • ADAR-mediated editing is a likely mechanism driving the observed U-to-C and A-to-G transitions in NoVs.
  • Understanding NoV mutation dynamics is crucial for controlling viral evolution and immune escape.