Bacteriophage genomics

Abstract

The past three years have seen an escalation in the number of sequenced bacteriophage genomes with more than 500 now in the NCBI phage database, representing a more than threefold increase since 2005. These span at least 70 different bacterial hosts, with two-thirds of the sequenced genomes of phages representing only eight bacterial hosts. Three key features emerge from the comparative analysis of these genomes. First, they span a very high degree of genetic diversity, suggesting early evolutionary origins. Second, the genome architectures are mosaic, reflecting an unusually high degree of horizontal genetic exchange in their evolution. Third, phage genomes contain a very high proportion of novel genetic sequences of unknown function, and probably represent the largest reservoir of unexplored genes. With an estimated 10(31) bacterial and archael viruses in the biosphere, our view of the virosphere will draw into sharper focus as further bacteriophage genomes are characterized.

Figure 1. Size distribution of sequenced bacteriophage genomes

As of early July 2008, the phage database at NCBI contains 500 genomes ranging from 2.3 kbp to 316 kbp. The numbers of sequenced genomes in each size range is shown. Size intervals are 5 kbp from 2−100 kbp, and 25 kbp from 100−300 kbp.

Figure 2. Nucleotide sequence relationships among phages infecting common bacterial hosts

Bacteriophage genomes of 30 Pseudomonas and 50 mycobacteriophages were concatenated and compared using the program Gepard. The comparison illustrates two key points. First, that there are groups of genomes within each set that share significant nucleotide sequence similarity, while there is no detectable sequence similarity between the two groups (data not shown). Secondly, even within phages infecting a common host, there is enormous genetic diversity.

Figure 3. Phage genome mosaicism at the nucleotide and protein sequence levels

A. Nucleotide sequence comparison of mycobacteriophages Cjw1 and 244. The two annotated genomes [29] were aligned using the Artemis Comparison Tool, and highly related sequences shown by red shading. The correspondence of nucleotide discontinuities with gene boundaries is evident. B. Phamily circles of thee consecutive genes (62−64) of mycobacteriophage Giles [24,33]. Each circle corresponds to three different Phams representing group of related proteins; and the thickness of the lines connecting each phamily constituent is related to the strengths of the relationships. Each of the three Giles genes clearly has a different evolutionary history.