The Tandem Repeats Enabling Reversible Switching between the Two Phases of β-Lactamase Substrate Spectrum

Hyojeong Yi, Han Song, Junghyun Hwang, Karan Kim, William C. Nierman, Heenam Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Expansion or shrinkage of existing tandem repeats (TRs) associated with various biological processes has been actively studied in both prokaryotic and eukaryotic genomes, while their origin and biological implications remain mostly unknown. Here we describe various duplications (de novo TRs) that occurred in the coding region of a β-lactamase gene, where a conserved structure called the omega loop is encoded. These duplications that occurred under selection using ceftazidime conferred substrate spectrum extension to include the antibiotic. Under selective pressure with one of the original substrates (amoxicillin), a high level of reversion occurred in the mutant β-lactamase genes completing a cycle back to the original substrate spectrum. The de novo TRs coupled with reversion makes a genetic toggling mechanism enabling reversible switching between the two phases of the substrate spectrum of β-lactamases. This toggle exemplifies the effective adaptation of de novo TRs for enhanced bacterial survival. We found pairs of direct repeats that mediated the DNA duplication (TR formation). In addition, we found different duos of sequences that mediated the DNA duplication. These novel elements—that we named SCSs (same-strand complementary sequences)—were also found associated with β-lactamase TR mutations from clinical isolates. Both direct repeats and SCSs had a high correlation with TRs in diverse bacterial genomes throughout the major phylogenetic lineages, suggesting that they comprise a fundamental mechanism shaping the bacterial evolution.

Original languageEnglish
JournalPLoS Genetics
Volume10
Issue number9
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Tandem Repeat Sequences
tandem repeat sequences
substrate
genome
Nucleic Acid Repetitive Sequences
DNA
gene
biological processes
antibiotics
mutation
Bacterial Genomes
Biological Phenomena
Ceftazidime
amoxicillin
phylogenetics
Amoxicillin
shrinkage
Genes
genes
Genome

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

The Tandem Repeats Enabling Reversible Switching between the Two Phases of β-Lactamase Substrate Spectrum. / Yi, Hyojeong; Song, Han; Hwang, Junghyun; Kim, Karan; Nierman, William C.; Kim, Heenam.

In: PLoS Genetics, Vol. 10, No. 9, 01.01.2014.

Research output: Contribution to journalArticle

Yi, Hyojeong ; Song, Han ; Hwang, Junghyun ; Kim, Karan ; Nierman, William C. ; Kim, Heenam. / The Tandem Repeats Enabling Reversible Switching between the Two Phases of β-Lactamase Substrate Spectrum. In: PLoS Genetics. 2014 ; Vol. 10, No. 9.
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