The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum.
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 oc...
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2014-09-01
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doaj-f05d760cfb9342f2b0e2c425d10a50a92020-11-25T01:01:28ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-09-01109e100464010.1371/journal.pgen.1004640The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum.Hyojeong YiHan SongJunghyun HwangKaran KimWilliam C NiermanHeenam Stanley KimExpansion 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.http://europepmc.org/articles/PMC4169377?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hyojeong Yi Han Song Junghyun Hwang Karan Kim William C Nierman Heenam Stanley Kim |
spellingShingle |
Hyojeong Yi Han Song Junghyun Hwang Karan Kim William C Nierman Heenam Stanley Kim The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. PLoS Genetics |
author_facet |
Hyojeong Yi Han Song Junghyun Hwang Karan Kim William C Nierman Heenam Stanley Kim |
author_sort |
Hyojeong Yi |
title |
The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
title_short |
The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
title_full |
The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
title_fullStr |
The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
title_full_unstemmed |
The tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
title_sort |
tandem repeats enabling reversible switching between the two phases of β-lactamase substrate spectrum. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2014-09-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4169377?pdf=render |
work_keys_str_mv |
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