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A Rapid Image-based Bacterial Virulence Assay Using Amoeba
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Gene inversion potentiates bacterial evolvability and virulence.

Christopher N Merrikh1, Houra Merrikh2,3

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Bacterial genes typically align with replication direction to prevent conflicts. However, this study reveals many genes invert, increasing head-on collisions and potentially enhancing bacterial evolution and pathogenicity.

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Area of Science:

  • Microbial genetics
  • Evolutionary biology
  • Molecular biology

Background:

  • Most bacterial genes are encoded on the leading strand, co-orienting replication machinery and RNA polymerases.
  • This co-orientation minimizes detrimental head-on collisions between replication and transcription machineries.
  • Selection is expected to favor co-orientation, reducing head-on gene arrangements.

Purpose of the Study:

  • To investigate the evolutionary dynamics of gene orientation in bacterial genomes.
  • To challenge the prevailing model that selection strictly favors co-oriented genes.
  • To explore the functional implications of head-on gene arrangements.

Main Methods:

  • Analysis of the evolutionary inversion record of chromosomally encoded genes using GC skew calculation.
  • Comparative genomic analysis across multiple divergent bacterial pathogens.
  • Assessment of mutation rates (dN/dS) and selection pressures on head-on genes.

Main Results:

  • A significant number of previously co-oriented genes have inverted to a head-on orientation.
  • Head-on gene arrangements appear to increase replication-transcription conflicts.
  • Head-on genes, including those for antibiotic resistance and virulence, exhibit higher mutation rates and are under positive selection (dN/dS > 1).

Conclusions:

  • Spontaneous gene inversions can lead to head-on replication-transcription collisions.
  • These collisions may enhance bacterial evolvability by increasing mutation rates and positive selection.
  • Gene inversions and subsequent head-on arrangements could contribute to increased bacterial pathogenicity.