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Genome-Wide Methylation in Human Microbiome Samples

Monday, August 18, 2014

Scientists in Florida and Finland recently published a report of their work studying methylation patterns in two human microbiome samples. While microbiome studies have become quite popular, the authors note there have been no prior papers detailing genome-wide methylation of bacteria found in those studies. Their goal was to ascertain how much added functional variation might occur based on methylation patterns.

The methylome of the gut microbiome: disparate Dam methylation patterns in intestinal Bacteroides dorei,” published in Frontiers in Microbiology, comes from lead author Michael Leonard and senior author Eric Triplett at the University of Florida plus a team of collaborators from hospitals and universities across Finland.

The scientists used Single Molecule, Real-Time (SMRT®) Sequencing for its ability not just to sequence bacterial genomes to closure, but also to read methylation patterns across those genomes. They studied two stool samples from children at high risk for developing type 1 diabetes; both stool samples were dominated by Bacteroides dorei. In both strains, after sequencing to closure using the PacBio® sequencer, the team looked at GATC motifs for Dam methylation, which is believed to change gene expression in bacteria.

A marked difference between the genomes was discovered during methylation analysis: the first strain lacked Dam methylation entirely, while the second contained more than 20,000 methylated GATC sites. (Indeed, that strain only had three GATC sites that were not found to be methylated.) Scientists determined that the first genome lacked the DamMT gene, though both strains had other methylation patterns. “Another interesting observation is that of all of the methylation motifs observed in these two genomes, none is methylated in both genomes,” the authors report. “This suggests that the primary source of methyltransferases in these genomes is through lateral transfer, often from phage.”

Based on these remarkable differences, the scientists conclude that DNA sequence alone is not enough to understand the function of bacterial strains in a microbiome sample. “This work suggests that future microbiome studies should consider the methylome when describing the bacterial diversity in the gut,” the authors write. “Such analyses are no longer difficult given the latest sequencing technologies.”

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