New dimensions of the virus world discovered through metagenomics

Metagenomics Over the past two decades, the study of marine viruses using electron and fluorescent microscopy revealed an unexpected abundance of virus particles. At 106 to 109 particles per milliliter of sea water, viruses are the most abundant microbes in the sea and, most likely, in the entire biosphere. Furthermore, they have emerged as crucial geochemical and ecological factors in marine ecosystems. More recently, extensive data on the metagenomics of marine viruses have been reported. Viral metagenomics is either pursued specifically by deep sequencing of environmental samples enriched for virus particles or emerge serendipitously through detection of virus-specific sequences in databases yielded by other metagenomic projects. The latter type of study is mostly limited to known classes of viruses but the former has the potential to discover completely unknown viruses.

The gene repertoires of the putative marine viromes that were derived by sequencing double-stranded DNA (dsDNA) isolated from the fractions enriched for virus-like particles brought several major surprises and potential concerns. In particular, the estimates of the number of unique viral genotypes yielded breathtaking numbers of >1030, making the marine viromes the most genetically diverse biological communities on earth. The main and highly unexpected findings were that a substantial majority of the putative viral sequences were not significantly similar to any sequences in the current databases, and that those sequences that did have detectable homologs represented, primarily, various bacterial genes often having specific roles in central metabolism rather than distinct classes of genes commonly found in known bacteriophages or other viruses. These remarkable findings suggest two possibilities that are not mutually exclusive. First, known viruses might not be representative of actual viromes, with the implication that marine viruses are the principal reservoir of new genes in the ocean. Second, the samples deemed to represent viromes might be, largely, not of viral origin and reflect contamination of the samples with non-viral DNA, which would indicate a serious shortcoming of the current metagenomic protocols.

This paper applies computational approaches to analyze the marine dsDNA viromes and shows that, despite non-negligible contamination with bacterial genes, these sequences represent a collection that is markedly different in its statistical features from both prokaryotic and known viral genomes. Thus, there seems to be a realistic possibility that the actual marine viromes consist predominantly of virus-like particles that are different from well-characterized phages and might resemble gene transfer agents (GTAs). Although still a young field, metagenomics is already revealing unexpected yet fundamental features of the virus world.

New dimensions of the virus world discovered through metagenomics. Trends Microbiol. Nov 24 2009
Metagenomic analysis of viruses suggests novel patterns of evolution, changes the existing ideas of the composition of the virus world and reveals novel groups of viruses and virus-like agents. The gene composition of the marine DNA virome is dramatically different from that of known bacteriophages. The virome is dominated by rare genes, many of which might be contained within virus-like entities such as gene transfer agents. Analysis of marine metagenomes thought to consist mostly of bacterial genes revealed a variety of sequences homologous to conserved genes of eukaryotic nucleocytoplasmic large DNA viruses, resulting in the discovery of diverse members of previously undersampled groups and suggesting the existence of new classes of virus-like agents. Unexpectedly, metagenomics of marine RNA viruses showed that representatives of only one superfamily of eukaryotic viruses, the picorna-like viruses, dominate the RNA virome.

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