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Related Concept Videos

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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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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Measuring Microbial Mutation Rates with the Fluctuation Assay
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Published on: November 28, 2019

Evidence for mutation showers.

Jicheng Wang1, Kelly D Gonzalez, William A Scaringe

  • 1Department of Molecular Genetics and Bioinformatics Group, Department of Molecular Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 9, 2007
PubMed
Summary

Mutation showers, clusters of multiple mutations, occur frequently in Big Blue mice. These events, spanning kilobases, have significant implications for cancer development and evolution.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Transgenic Models

Background:

  • Big Blue transgenic mice exhibit spontaneous clustered mutations at high frequencies.
  • These mutations suggest chronocoordinate mutational events.

Purpose of the Study:

  • To investigate the existence and extent of "mutation showers" – chronocoordinate mutations spanning multiple kilobases.
  • To determine the frequency and characteristics of these mutation showers.

Main Methods:

  • Sequencing of the lacI gene region and flanking sequences (10.7 kb) in Big Blue mouse mutants.
  • Analysis of mutation distribution and spacing, including remote regions (8.5 kb).

Main Results:

  • Mutants with multiple lacI mutations showed significantly more "ectomutations" in flanking regions compared to single-mutation mutants (P < 0.0001).
  • Mutation showers averaged one mutation per 3 kb, with significant clustering observed.
  • Mutation showers generally extended up to approximately 30 kb.

Conclusions:

  • Mutation showers are confirmed as a distinct mutational event in this system, constituting at least 0.2% of events.
  • These findings suggest potential for rapid oncogenesis ("cancer in an instant") and highlight the role of introns in mitigating mutation impacts.