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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

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Published on: May 2, 2018

Non-canonical gene amplifications facilitate adaptive evolution in bacteria.

Idan Yelin¹, Roy Kishony^2,3,4,5

¹Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.

Nature Microbiology

|July 6, 2026

Summary

Non-canonical gene amplifications, driven by single insertion sequence (IS) elements, are the most common type in bacteria. This study introduces AmpliFinder, revealing their crucial role in bacterial adaptation and antibiotic resistance.

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Area of Science:

Microbiology
Genetics
Evolutionary Biology

Background:

Gene amplification is a key bacterial adaptation mechanism.
Insertion sequence (IS) elements mediate gene amplification through recombination.
Non-canonical amplifications, involving a single IS element, are proposed but their prevalence and role are unclear.

Purpose of the Study:

To develop a computational tool, AmpliFinder, for identifying non-canonical IS-associated amplifications.
To investigate the prevalence and abundance of non-canonical amplifications in bacteria.
To understand the role of non-canonical amplifications in bacterial adaptive evolution, particularly concerning antibiotic resistance.

Main Methods:

Development of AmpliFinder, a computational tool utilizing short-read sequencing data.
Systematic identification of IS-chromosome junctions corresponding to single IS elements.
Application of AmpliFinder to 10,347 laboratory-evolved Escherichia coli and Acinetobacter baumannii isolates.
Validation of inferred amplification structures using ultra-long-read sequencing.

Main Results:

Identified 113 distinct de novo IS-associated amplifications.
Found non-canonical amplifications to be the most abundant mode of amplification.
Proposed a model for non-canonical amplification formation, supported by intermediate structures.
Demonstrated that non-canonical amplifications more effectively amplify antibiotic-resistance genes under selection.

Conclusions:

Non-canonical IS-based amplifications are prevalent and abundant in bacteria.
These amplifications play a significant role in bacterial adaptive evolution.
Non-canonical amplifications provide a targeted mechanism for acquiring adaptive traits, such as antibiotic resistance.