The evolution of mobile genetic elements in Gram-negative bacteria

I will explore how structural variation can be used to understand the evolution of antimicrobial resistance (AMR) on mobile genetic elements (MGEs). Most previous research is biased towards nucleotide-level variations in the core genome (high-effect SNPs).

Now, the availability of complete genomes means that resolving the larger structural variation of MGEs is both possible and increasingly relevant for the spread of AMR.

I will develop a framework to model the non-mutational processes which generate this variation, then apply this to the linked evolution of MGEs and their ‘host’ genomes. During this fellowship, I will sequentially: - Aim 1.

Develop a tool to quantify structural variation and resolve common blocks around the flanking region of AMR genes, which I have previously shown can be used for phylogenetic reconstruction. - Aim 2. Apply this to longitudinal datasets and obtain rate estimates for non-mutational processes. - Aim 3. Investigate the compensatory evolution of MGEs as they move between genomic backgrounds.

Two major applications will be: - Application 1. Small transposons, leading on from my pioneering work on the mcr-1 transposon. - Application 2. Clinical class 1 integrons, which carry multiple AMR genes. This proposal tackles questions of fundamental importance for the evolution of flexible genomes.