Bacteriophage genomics

Abstract

Comparative genomic studies of bacteriophages, especially the tailed phages, together with environmental studies, give a dramatic new picture of the size, genetic structure and dynamics of this population. Sequence comparisons reveal some of the detailed mechanisms by which these viruses evolve and influence the evolution of their bacterial and archaeal hosts. We see rampant horizontal exchange of sequences among genomes, mediated by both homologous and nonhomologous recombination. High frequency exchange among phages occupying similar ecological niches leads to a high degree of mosaic diversity in local populations. Horizontal exchange also takes place at lower frequency across the entire span of phage sequence space.

Introduction

Suppose we were to stop an average molecular biologist on the street and ask what kinds of bacteriophages there are on Earth. The answer would certainly include T4, the T. rex of the phage world, as well as the well studied temperate phage λ. Most respondents would remember that there are other similar temperate phages, including some such as Salmonella phage P22 that infect non-Escherichia coli bacteria, and most would also know that there is a phage called T7 whose raison d’être is to supply promoters and a special RNA polymerase for expression vectors. The more sophisticated molecular biologists might recall that there are actually dozens of other phages that infect bacteria such as Bacillus and Vibrio, and that there are also some curious small phages, such as φX174, MS2 and M13, that lack tails and have genomes that are not dsDNA. Such a response would not be very different from what we would have heard had we conducted our survey a decade ago. Yet as readers who have been paying attention will know, over the past 10 years, and especially over the past 3–5 years, there has been a revolutionary change in our understanding of the nature and size of the global phage population, of the mechanisms and dynamics by which the phages evolve, and of the enormous impact phages have on terrestrial biology and biogeochemistry, and on the ecology and evolution of their bacterial and archaeal hosts.

Our new view of these matters comes primarily from two advances: first, a new appreciation of the abundance of tailed phages in the environment and of the dynamic nature of that population, and second, the recent availability of a significant number of phage genome sequences. Direct measurements of the abundance of tailed phages in the environment indicate ∼10⁷ particles/ml in coastal seawater and even higher numbers in some freshwater sources [1] (see Figure 1). The global population is estimated to be on the order of 10³¹ individuals: if they were laid end to end, they would span between the Earth and the Sun 10¹³ times. This population turns over every few days [2], from which it can be calculated that the number of phages initiating an infection somewhere on Earth every second is on the order of Avagadro’s number. Numbers like these give a new impression of the opportunities for genetic exchange in the phage population, particularly because most bacterial cells contain prophage DNA with which the infecting phage can interact. At the laboratory end of things there are now about 150 complete genome sequences of tailed phages in the databases, and this number is increasing rapidly. At first blush, 150 genome sequences appears to be a hopelessly miniscule sampling of the population, but as described below, there are beginning to be indications that, as a result of extensive horizontal exchange of sequences across the population, we have already seen an appreciable fraction — if still a small minority — of all phage gene sequence families.