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What is the definition of a metagenome?

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The term “metagenome” is frequently invoked during reports on the study of the human microbiome. Unfortunately, it seems to have different meanings to various authors, which understandably leads to some confusion.

In my mind, a metagenome refers to the genomic contents of an entire microbial community. This means that metagenomic sequencing involves the generation of whole genome sequence data from community-acquired DNA, most usually through shotgun sequencing. I do not think that sequencing DNA obtained through PCR amplification of the small subunit ribosomal RNA locus (SSU-rRNA) constitutes metagenomic sequencing. I also do not think that our microbiome is the same thing as our metagenome. Rather, the metagenome is an important component of the microbiome (see this link for more).

Other authors certainly disagree with me on these points. But, the historical literature aligns with my interpretation. The earliest reference that I can find to “metagenome” in NCBI’s PubMed is a 1998 Chemistry and Biology paper by Jo Handlesman and colleagues entitled “Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products.” In it, the authors describe a clone-library based method that enables exploration of the biological functions encoded in the genomes of the microbes that make up a soil community:

The methodology has been made possible by advances in molecular biology and eukaryotic genomics, which have laid the groundwork for cloning and functional analysis of the collective genomes of soil microflora, which we term the metagenome of the soil.

Handlesman and colleagues refer to the metagenome as the collective genome of a microbial community and point to the ability to infer the biology functions of these microbes from this data. This transcends the evaluation of a single locus whose DNA sequence was obtained via PCR amplification.

Admittedly, the SSU-rRNA locus is part of the genome. As a result, it may be fair for one to argue that an analysis of the collection of PCR-amplified SSU-rRNA sequences that have been obtained from a microbial community constitutes a metagenomic analysis. However, given that the methods needed to analyze PCR-amplified SSU-rRNA data are very different from those needed to analyze whole-genomic/shotgun sequence data obtained from a community — as are, frequently, the points of investigation — and given the rapid growth in the number of studies applying these two different sequencing strategies, I think it is important to disambiguate the term “metagenome”. Otherwise, we risk confusing readers and students of the field.

So, when you see me refer to a metagenome, it will be in regards to the sum total of the genomic information that is encompassed by all of an organisms in a community.

Written by sharpton

August 14th, 2012 at 8:56 pm

Posted in definitions

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