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Researchers Sequence Pan Genome of Gut Archaeal Species

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a paper set to appear online this week in the Proceedings of the National Academy of Sciences, researchers from Washington University and elsewhere reported that have sequenced the pan genome of the hydrogen-consuming gut archaea Methanobrevibacter smithii.

By sequencing M. smithii strains from fecal samples taken from identical and non-identical twins, the team was able to identify core genes shared across M. smithii strains as well as those present in only some strains. They also used RNA sequencing to look at how the expression changes in the archaeal species depending on its environment — and to detect groups of bacteria associated with certain strains.

In particular, their findings point to a group of adhesin-like protein coding genes in the M. smithii pan genome that vary from one strain to the next and seem to influence M. smithii's interactions with other microbes.

"We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches," senior author Jeffrey Gordon, a researcher with Washington University School of Medicine's Center for Genome Sciences, and his co-authors wrote, "by allowing them to establish syntrophic relationships with bacterial partners with different metabolic capabilities and patterns of co-occurrence."

M. smithii is an archaeal species that consumes hydrogen in the human gut, the researchers explained. Since hydrogen produced during fermentation of food by bacteria in the gut affects the activity of some bacterial enzymes, they added, this hydrogen use contributes to the energy produced from food.

"[M]anipulation of the abundance of hydrogen consumers or their metabolic activities could affect the efficiency of energy harvest by the host," they wrote, noting that M. smithii may serve as an attractive therapeutic target for those interested in tweaking how energy gets harvested from food.

In an effort to better understand the microbe and its interactions in the gut, Gordon and his colleagues first determined which subjects were carrying hydrogen-consuming methanogens using a quantitative PCR assay targeting the methyl coenzyme M reductase subunit A, or mcrA. In general, they noted, past studies hint that between about a third and half of individuals carry these sorts of methane-producing microbes.

When they tested fecal samples from 40 identical and 28 non-identical female adult twin pairs born in Missouri, the researchers found that 23 percent of individuals tested had detectable levels of methanogens.

They also found comparable patterns when they tested 51 of the twins' mothers: 31 percent of the mothers tested carried detectable levels of methanogens, though the presence of these bugs in mothers was not significantly linked to their occurrence in twin daughters.

Identical twins were more likely to both carry methanogens than their non-identical counterparts, suggesting that host genetics do have some influence on the presence or absence of these microbes.

When the team did 16S rRNA sequencing to pinpoint other microbes present in the fecal samples with these methanogens, they identified 22 bacterial species — many from the class Clostridiales — that tend to crop up in the same samples.

They then sequenced the genomes of 20 different M. smithii isolated from twins and their mothers using the Illumina GAIIX and the Roche 454 GS FLX Titanium and did RNA sequencing for 23 M. smithii isolates to discern the effects that various concentrations of hydrogen and the methane-related compound formate have on gene expression patterns.

In so doing, the researchers found a core group of 987 genes that were conserved amongst all M. smithii strains tested, along with another 1,860 genes that were found in some strains but not others. Nearly 93 percent of SNPs seem to overlap between any two of the strains.

Samples from both the identical and non-identical twin pairs showed more M. smithii gene and SNP overlap than samples collected from other family members, they reported, though samples from the same families generally clustered with one another.

The team's experiments also pointed to more than 100 adhesin-like protein genes that appear to be differentially present and expressed in hydrogen-consuming archaea.

"None of the [ALP] genes are formate-responsive but members of each [operational gene unit] exhibit strain-specific difference in their levels of expression," the researchers wrote.

In particular, they explained, these ALPs seem to mediate interactions between the bug and nearby bacteria with their own metabolic specialties. Based on these patterns, the authors speculated, "M. smithii strains use their different repertoires of ALPs and the different sensitivities of ALP genes to formate to create diversity in their physical locations and/or their metabolic niches within the gut."

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