Methylome Diversification through Changes in DNA Methyltransferase Sequence Specificity

Abstract

Epigenetic modifications such as DNA methylation have large effects on gene expression and genome maintenance. Helicobacter pylori, a human gastric pathogen, has a large number of DNA methyltransferase genes, with different strains having unique repertoires. Previous genome comparisons suggested that these methyltransferases often change DNA sequence specificity through domain movement—the movement between and within genes of coding sequences of target recognition domains. Using single-molecule real-time sequencing technology, which detects N6-methyladenines and N4-methylcytosines with single-base resolution, we studied methylated DNA sites throughout the H. pylori genome for several closely related strains. Overall, the methylome was highly variable among closely related strains. Hypermethylated regions were found, for example, in rpoB gene for RNA polymerase. We identified DNA sequence motifs for methylation and then assigned each of them to a specific homology group of the target recognition domains in the specificity-determining genes for Type I and other restriction-modification systems. These results supported proposed mechanisms for sequence-specificity changes in DNA methyltransferases. Knocking out one of the Type I specificity genes led to transcriptome changes, which suggested its role in gene expression. These results are consistent with the concept of evolution driven by DNA methylation, in which changes in the methylome lead to changes in the transcriptome and potentially to changes in phenotype, providing targets for natural or artificial selection.

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori

“…A recent study by Furuta et al (2014) used a genomic approach to compare methylation profiles of closely related H. pylori strains and showed outstanding diversity of methylation sequence-specificity across lineages. As methylation is an epigenetic mechanism responsible for the regulation of gene expression and phenotypic plasticity, the identification of certain selected methylation genes encourage the study of their specific role and their evolutionary implications in H. pylori methylation patterns.…”

Serology

“…The same group in collaboration with researchers in Iran was able to identify an H. pylori protein, FliD, essential in the assembly of the fl agella [ 2 ]. The recombinant FliD protein was tested on a group of 618 patients (51.4 % H. pylori positive) with 97.4 % sensitivity and 99 % specifi city using a line assay and 97 % and 96 % by ELISA, respectively [ 20 ]. Other attempts to select antigenic proteins of potential diagnostic value were made (CafI, UBT urea breath test …”

Crystal structure of a novel domain of the motor subunit of the Type I restriction enzyme EcoR124 involved in complex assembly and DNA binding

“…bacteriophages) or by methylating the daughter DNA strand generated during the preceding replication event, thereby protecting the cell's own DNA from degradation. R-M enzymes have also been implicated in horizontal gene transfer (3), differential gene expression through epigenetic modification (4,5) and driving divergent evolution (6,7). The practical impact of R-M enzymes on genetic engineering and DNA fingerprinting can hardly be overstated (8).…”