Complexity: phage genomics
Are phages genetically as diverse as they are numerous in the biosphere? Only a few phage groups have been intensively studied by sequencing projects (coliphages, mycobacteriophages, and dairy phages). These investigations demonstrated that the genetic relatedness between phages reflected more the phylogenetic relationships between their host bacteria than the possibilities of current gene transfer in a given ecological setting. For example, phages from dairy streptococci were closely related to phages from pathogenic streptococci living on the skin. Lactococcus phages are the prime cause of cheese fermentation failures. Due to this economic interest, their genetic diversity was intensively explored. Different types of prolate-headed and large and small isometric-headed Siphoviridae (phages with long noncontractile tails) and rare Podoviridae (phages with short tails) were described. Interlaboratory phage comparisons led to the definition of 12 lactococcal phage species. In meat fermentation, you also find Myoviridae (phages with contractile tails) infecting Lactobacillus starters (see Fig. 2 for the basic tailed phage types). Mycobacteria are hosts to an amazingly diverse group of phages (51). Their morphology stimulated the researchers to use such fanciful names as Corndog phage. As variable as the morphologies are, their genomes are just as variable. Within the 14 sequenced mycobacteriophages, 10 lacked DNA sequence similarity with the other mycobacteriophages, and nearly half of the predicted proteins lacked any database matches. The workhorses of molecular bacteriology, Escherichia coli and Bacillus subtilis, are also hosts to about 10 phages with fundamentally different genome organization, not to mention substantial differences at the DNA sequence level within each group of phages. If these observations of 10 or more phages per bacterial species can be generalized, phages might indeed represent the largest unexplored reservoir of sequence information in the biosphere. Random sequencing efforts of viral DNA from two uncultured marine water samples (10) combined with a statistical analysis revealed between 400 and 7,000 different viral types in the two investigated 100-liter samples, with the most abundant type representing 3% of the total viral population. However, a different picture was obtained by the few complete marine phage genomes. This analysis led to the description of a new phage family (Corticoviridae), while other marine phages shared protein sequence similarity with coliphages T7, T4, lambda, P2, and dairy siphophages, suggesting a limited number of prototype phage genomes (18, 72) (Fig. 3).
The human gastrointestinal tract is rich in commensal life forms. About 1011
bacteria per ml of colonic content are normally found. The number of bacterial cells in the gut exceeds the total number of cells constituting the human body. Gut bacteria contain about 400 bacterial species, but only 40 species account for 99% of the total population. Also, shotgun cloning of the uncultured virus fraction of human feces underlined the genetic diversity of this fraction (9
). Statistical calculations suggested between 160 and 1,200 viral genotypes in the intestine.