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Measuring Microbial Mutation Rates with the Fluctuation Assay
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Transfer RNA genes experience exceptionally elevated mutation rates.

Bryan P Thornlow1, Josh Hough1, Jacquelyn M Roger1

  • 1Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064.

Proceedings of the National Academy of Sciences of the United States of America
|August 22, 2018
PubMed
Summary
This summary is machine-generated.

Transfer RNAs (tRNAs) are vital for protein synthesis. Our study reveals that high transcription rates drive mutations in tRNA genes, but strong selection preserves their function, impacting human health.

Keywords:
TAMcomputational predictionmutagenesistRNAtranscription

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genetics

Background:

  • Transfer RNAs (tRNAs) are essential for protein synthesis and are highly conserved across species.
  • The evolutionary pressures shaping tRNA genes remain largely unknown.
  • Understanding tRNA evolution is crucial for comprehending fundamental cellular processes.

Purpose of the Study:

  • To investigate the evolutionary forces, specifically transcription-associated mutagenesis and selection, acting on tRNA genes.
  • To determine the mutation rates and selective pressures at tRNA loci compared to the nuclear genome average.
  • To explore the relationship between tRNA expression levels and mutation rates in flanking regions.

Main Methods:

  • Comparative evolutionary analyses of tRNA genes and their flanking sequences in humans and model organisms.
  • Mutation rate estimation at tRNA loci.
  • Assessment of purifying selection acting on tRNA genes versus non-coding regions.
  • Correlation analysis between tRNA expression levels and local mutation rates.

Main Results:

  • Mutation rates at broadly expressed cytosolic tRNA genes are 7-10 times higher than the nuclear genome average.
  • Strong purifying selection acts on tRNA genes, counteracting the elevated mutation rate.
  • A positive correlation exists between tRNA expression levels and mutation rates in adjacent genomic regions.
  • Mutations at tRNA loci contribute significantly to the overall mutational load.

Conclusions:

  • Transcription-associated mutagenesis and strong purifying selection are key drivers of tRNA gene evolution.
  • Elevated mutation rates at tRNA loci have implications for mutational load and fitness in human populations.
  • The correlation between expression and mutation rate offers a potential method for estimating tRNA gene activity.