Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria

Rohan Maddamsetti, Yi Yao, Teng Wang, Junheng Gao, Vincent T. Huang, Grayson S. Hamrick, Hye-In Son and Lingchong You ()
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Rohan Maddamsetti: Duke University
Yi Yao: Duke University
Teng Wang: Duke University
Junheng Gao: Duke University School of Medicine
Vincent T. Huang: Duke University
Grayson S. Hamrick: Duke University
Hye-In Son: Duke University
Lingchong You: Duke University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.

Date: 2024
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DOI: 10.1038/s41467-024-45638-9

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