BackgroundDiversity Generating Retroelements (DGRs) are genetic cassettes that can introduce tremendous diversity into a short, defined region of the genome. They achieve hypermutation through replacement of the variable region with a strongly mutated cDNA copy generated by the element-encoded reverse transcriptase. In contrast to “selfish” retroelements such as group II introns and retrotransposons, DGRs impart an advantage to their host by increasing its adaptive potential. DGRs were discovered in a bacteriophage, but since then additional examples have been identified in some bacterial genomes.ResultsHere we present the program DiGReF that allowed us to comprehensively screen available databases for DGRs. We identified 155 DGRs which are found in all major classes of bacteria, though exhibiting sporadic distribution across species. Phylogenetic analysis and sequence comparison showed that DGRs move between genomes by associating with various mobile elements such as phages, transposons and plasmids. The DGR cassettes exhibit high flexibility in the arrangement of their components and easily acquire additional paralogous target genes. Surprisingly, the genomic data alone provide new insights into the molecular mechanism of DGRs. Most notably, our data suggest that the template RNA is transcribed separately from the rest of the element.ConclusionsDiGReF is a valuable tool to detect DGRs in genome data. Its output allows comprehensive analysis of various aspects of DGR biology, thus deepening our understanding of the role DGRs play in prokaryotic genome plasticity, from the global down to the molecular level.
Background and Purpose—
Dental and periodontal disease are potentially involved in the pathogenesis of atherosclerosis. We investigated whether dental and periodontal status is associated with the presence and future progression of carotid stenosis.
Methods—
We randomly selected 411 of 1268 participants from the prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and evaluated dental and periodontal status and oral hygiene at baseline measuring three World Health Organization-validated indices: DMFT (decayed, missing, filled teeth), SLI (Silness-Löe Index), and CPITN (community periodontal index for treatment needs), respectively. The degree of carotid stenosis was measured by duplex ultrasound at baseline and after median 7.5 months (range=6 to 9 months) to identify patients with progressive carotid stenosis.
Results—
DMFT (
P
<0.01), SLI (
P
=0.048), CPITN (
P
=0.007), and edentulousness (
P
=0.007) were associated with the baseline degree of carotid stenosis. Atherosclerosis progression was observed in 48 of 411 patients (11.7%). DMFT (adjusted odds ratio [OR]=1.11, 95% CI=1.01 to 1.22,
P
=0.032) and SLI (adjusted OR=1.77, 95% CI=1.09 to 2.79,
P
=0.021), but not CPITN (adjusted OR=1.51, 95% CI=0.89 to 2.45,
P
=0.16) were significant predictors of disease progression, irrespective of traditional cardiovascular risk factors and the baseline degree of stenosis. Edentulous patients had a significantly increased risk for disease progression as compared with patients with teeth (adjusted OR=2.10, 95% CI=1.06 to 4.16,
P
=0.33).
Conclusion—
Dental status, oral hygiene, and particularly tooth loss are associated with the degree of carotid stenosis and predict future progression of the disease.
The insertion of a retrotransposable element is usually associated with adverse or, at best, neutral effects on the host. Diversity-generating retroelements (DGRs) are the first elements that seem to offer a direct selective advantage to their phage or prokaryote host by exact replacement of a short, defined region of a host gene with a hypermutated variant. In a previous study, we presented the software DiGReF for identification of DGRs in genome sequences, and compiled the first comprehensive set of diversity-generating retroelements in public databases. We identified 155 elements in more than 6000 prokaryotic and phage genomes, which was a surprisingly low number. In this commentary, we will discuss the low incidence of these elements and speculate about the biological role of bacterial DGRs.
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