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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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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Biased Mutation and Selection in RNA Viruses.

Talia Kustin1, Adi Stern1,2

  • 1The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, Israel.

Molecular Biology and Evolution
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RNA viruses exhibit adenine-rich (A-rich) genomes, a common evolutionary trait. This A-richness results from mutational biases and selection, potentially driven by host immune pressures across diverse RNA viruses.

Keywords:
RNA virusesphylogenyvirus evolution

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Area of Science:

  • Virology
  • Evolutionary Biology
  • Genomics

Background:

  • RNA viruses cause major pandemics like COVID-19 and Ebola.
  • High genetic diversity is a key challenge in controlling RNA viruses.
  • Despite diversity, RNA viruses share reliance on host cells and high mutation rates.

Purpose of the Study:

  • To identify shared evolutionary characteristics of RNA viruses.
  • To investigate the prevalence and drivers of skewed nucleotide composition in RNA viruses.
  • To understand the role of selection versus mutation in shaping viral genomes.

Main Methods:

  • Construction of a phylogeny-based dataset from thousands of diverse animal single-stranded RNA virus sequences.
  • Analysis of nucleotide composition, focusing on adenine-rich (A-rich) coding sequences.
  • Utilizing incomplete purifying selection at viral phylogenies' tips to differentiate mutation bias from selection.

Main Results:

  • The majority of studied RNA viruses display A-rich coding sequences.
  • Consistent mutational bias towards uracil (U) over adenine (A) was observed in all viral genomes.
  • +ssRNA viruses show selection against U and for A, creating A-rich genomes.
  • -ssRNA viruses exhibit U-bias on the negative strand, resulting in A-rich positive-strand coding sequences.

Conclusions:

  • A-richness in RNA viruses is a result of compensatory selection balancing mutational biases.
  • Factors like weakened RNA secondary structures, codon usage, and amino acid composition may contribute.
  • Host immune pressures are proposed as a driving force for convergent coding sequence composition biases in divergent RNA viruses.