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Horizontal gene transfer and evolution of antibiotic gene clusters
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Kallifidas, Dimitrios (2001) Horizontal gene transfer and evolution of antibiotic gene clusters. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b1377757~S1
Abstract
Genome sequencing projects from diverse bacteria and the release of genetically
engineered microorganisms make the topic of horizontal gene transfer (HGT)
fashionable. Sequence analysis indicates the high frequency and the importance of
horizontal gene transfer to the microbial evolution. Much knowledge about horizontal
transfer has been derived from studies using soil microcosms, fluorescent-marked donors
and recipients and from study of the increase of the antibiotic resistance as a result of use
and often abuse of antibiotics. However, little is known about the transfer of
chromosomally-located antibiotic biosynthesis genes in natural populations. The
streptomycin pathway-specific regulator, strR, has been found in a set of diverse
streptomycetes both phenotypically and genetically that previously have already been
described to carry the resistance (strA) and one biosynthetic (strBl) gene from the same
cluster. Phylogenetic analysis of both 16S rRNA and trpB gene fragments showed that
two isolates were closely related to S. coelicolor which are known not to produce
streptomycin or to contain any biosynthesis or resistance genes. The remaining pair did
appear to be closely related to each other, particularly from the trpB analysis. trpB gene
proved to be useful for resolving phylogenetic relationships between strains with highly
conserved gamma region of the 16S rRNA gene. However, one of these strains is the
only one from the S. griseus distant isolates that produced streptomycin and possessed
many other genes from the cluster. The phylogenetic incongruency between `species'
tree and `gene' tree can be attributed to horizontal gene transfer. The sequence identity
of the detected genes is extremely high (99%) indicating a recent transfer event. Besides
the physical proximity of strRABl genes, there is also a well-characterised functional
correlation of these genes in the streptomycin producer, S. griseus. However, strRA
genes are silent in coelicolor-like isolates ASSF15 and ASB37. Therefore, this transfer
may have other ecological role than a simple resistance phenotype such as the evolution
of antibiotic cluster. It was not possible to prove the integration site of strRABl genes
within ASB37 genome but a possible site was identified.
Pathway-specific regulator StrR activates the transcription of strBl and other
genes from the streptomycin cluster by binding to the upstream promoter regions. This
protein binds as a tetramer. N-terminal deleted StrR derivatives were still able to bind as
pseudodimers (two monomers). Two putative domains in the N'-terminus of the protein
responsible for the protein dimerisation during the binding process have been identified.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QR Microbiology | ||||
Library of Congress Subject Headings (LCSH): | Genetic transformation, Antibiotics -- Synthesis -- Genetic aspects, Streptomycin | ||||
Official Date: | September 2001 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Biological Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Wellington, E. M. H. (Elizabeth M. H.), 1954- | ||||
Sponsors: | Schering-Plough Corporation | ||||
Extent: | xiii, 187, [7] p. | ||||
Language: | eng |
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