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Volume 9, Issue 12

Visualizing and quantifying structural diversity around mobile resistance genes Open Access

Abstract

Understanding the evolution of mobile genes is important for understanding the spread of antimicrobial resistance (AMR). Many clinically important AMR genes have been mobilized by mobile genetic elements (MGEs) on the kilobase scale, such as integrons and transposons, which can integrate into both chromosomes and plasmids and lead to rapid spread of the gene through bacterial populations. Looking at the flanking regions of these mobile genes in diverse genomes can highlight common structures and reveal patterns of MGE spread. However, historically this has been a largely descriptive process, relying on gene annotation and expert knowledge. Here we describe a general method to visualize and quantify the structural diversity around genes using pangraph to find blocks of homologous sequence. We apply this method to a set of 12 clinically important beta-lactamase genes and provide interactive visualizations of their flanking regions at https://liampshaw.github.io/flanking-regions. We show that nucleotide-level variation in the mobile gene itself generally correlates with increased structural diversity in its flanking regions, demonstrating a relationship between rates of mutational evolution and rates of structural evolution, and find a bias for greater structural diversity upstream. Our framework is a starting point to investigate general rules that apply to the horizontal spread of new genes through bacterial populations.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): AMR , beta-lactamases , Enterobacterales , microbial evolution , mobile genetic elements and plasmids
Funding
This study was supported by the:
  • Wellcome Trust (Award 220422/Z/20/Z)
    • Principle Award Recipient: LiamP Shaw
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-12-20
2024-05-20
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Visualizing and quantifying structural diversity around mobile resistance genes
M Gen 9, 001168 (2023); https://doi.org/10.1099/mgen.0.001168
/content/journal/mgen/10.1099/mgen.0.001168
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