Visualizing and quantifying structural diversity around mobile resistance genes.

Shaw, Liam P; Neher, Richard A

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.

Citation

Shaw, L. P., & Neher, R. A. (2023). Visualizing and quantifying structural diversity around mobile resistance genes. Microbial Genomics, 9(12), 10.1099/mgen.0.001168. https://doi.org/10.1099/mgen.0.001168

• Journal Article Type: Article
• Acceptance Date: Dec 7, 2023
• Online Publication Date: Dec 20, 2023
• Publication Date: Dec 20, 2023
• Deposit Date: Jan 16, 2024
• Publicly Available Date: Jan 16, 2024
• Journal: Microbial genomics
• Electronic ISSN: 2057-5858
• Publisher: Microbiology Society
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 12
• Article Number: 001168
• Pages: 10.1099/mgen.0.001168
• DOI: https://doi.org/10.1099/mgen.0.001168
• Keywords: Bacteria - genetics, Integrons, Plasmids - genetics, beta-Lactamases - genetics, plasmids, beta-lactamases, mobile genetic elements, microbial evolution, Enterobacterales, AMR
• Public URL: https://durham-repository.worktribe.com/output/2085103