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DNA methylation assessed by SMRT sequencing is linked to mutations in Neisseria meningitidis isolates

Sater, Mohamad R. Abdul and Lamelas, Araceli and Wang, Guilin and Clark, Tyson A. and Röltgen, Katharina and Mane, Shrikant and Korlach, Jonas and Pluschke, Gerd and Schmid, Christoph D.. (2015) DNA methylation assessed by SMRT sequencing is linked to mutations in Neisseria meningitidis isolates. PLoS ONE, 10 (12). e0144612.

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Abstract

The Gram-negative bacterium Neisseria meningitidis features extensive genetic variability. To present, proposed virulence genotypes are also detected in isolates from asymptomatic carriers, indicating more complex mechanisms underlying variable colonization modes of N. meningitidis. We applied the Single Molecule, Real-Time (SMRT) sequencing method from Pacific Biosciences to assess the genome-wide DNA modification profiles of two genetically related N. meningitidis strains, both of serogroup A. The resulting DNA methylomes revealed clear divergences, represented by the detection of shared and of strain-specific DNA methylation target motifs. The positional distribution of these methylated target sites within the genomic sequences displayed clear biases, which suggest a functional role of DNA methylation related to the regulation of genes. DNA methylation in N. meningitidis has a likely underestimated potential for variability, as evidenced by a careful analysis of the ORF status of a panel of confirmed and predicted DNA methyltransferase genes in an extended collection of N. meningitidis strains of serogroup A. Based on high coverage short sequence reads, we find phase variability as a major contributor to the variability in DNA methylation. Taking into account the phase variable loci, the inferred functional status of DNA methyltransferase genes matched the observed methylation profiles. Towards an elucidation of presently incompletely characterized functional consequences of DNA methylation in N. meningitidis, we reveal a prominent colocalization of methylated bases with Single Nucleotide Polymorphisms (SNPs) detected within our genomic sequence collection. As a novel observation we report increased mutability also at 6mA methylated nucleotides, complementing mutational hotspots previously described at 5mC methylated nucleotides. These findings suggest a more diverse role of DNA methylation and Restriction-Modification (RM) systems in the evolution of prokaryotic genomes.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Molecular Immunology (Pluschke)
UniBasel Contributors:Pluschke, Gerd and Schmid, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:31 Aug 2018 06:39
Deposited On:13 Apr 2016 11:57

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