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Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes

Supriya Khedkar1, Georgy Smyshlyaev1,2, Ivica Letunic3

  • 1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany.

Nucleic Acids Research
|March 24, 2022
PubMed

Insights

Mobile genetic elements (MGEs) in prokaryotes, including transposons and phages, drive evolution and antibiotic resistance spread. Our framework unifies their analysis, revealing MGEs as major gene carriers and transfer agents across diverse bacteria.

Area of Science:

  • Microbiology
  • Genomics
  • Evolutionary Biology

Background:

  • Prokaryotic mobile genetic elements (MGEs) like transposons, integrons, phages, and plasmids are crucial for bacterial evolution and the spread of traits such as antibiotic resistance.
  • Current analysis of MGEs is fragmented, hindering a comprehensive understanding of their global distribution and evolutionary impact.

Purpose of the Study:

  • To develop a unified computational framework for identifying and analyzing diverse MGEs, their cargo genes, and horizontal transfer events in prokaryotes.
  • To provide a global overview of MGE prevalence, phylogenetic patterns, and environmental distribution.

Main Methods:

  • Developed a computational framework utilizing recombinases as MGE marker genes and pangenome data for boundary estimation.
  • Applied the framework to analyze approximately 84,000 prokaryotic genomes with habitat annotations.
  • Mapped millions of MGE-specific recombinases to categorize MGEs and quantify gene content and transfer events.

Main Results:

  • Identified 2.8 million MGE-specific recombinases across six operational MGE types, with MGEs comprising an average of 13% of a genome's genes.
  • Transposable elements (TEs) were the most abundant MGE type, followed by phages and phage-like elements.
  • Documented widespread MGE-mediated horizontal gene transfer across diverse bacteria and habitats, revealing significant hitchhiking of TEs and integrons with other MGEs.
  • Established TEs as the primary carriers of antibiotic resistance genes.

Conclusions:

  • The developed framework enables a holistic view of MGEs, their functions, and their role in bacterial evolution and adaptation.
  • Prokaryotic genomes are significantly shaped by MGEs, which are key drivers of horizontal gene transfer and the dissemination of critical traits like antibiotic resistance.
  • The proMGE resource (proMGE.embl.de) facilitates future research into the mobile fraction of prokaryotic genomes.

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