Reconstructing the modular recombination history of Staphylococcus aureus phages

Abstract

Background: Viruses that infect bacteria, called phages, are well-known for their extreme mosaicism, in which an individual genome shares many different parts with many others. The mechanisms for creating these mosaics are largely unknown but are believed to be recombinations, either illegitimate, or partly homologous. In order to reconstruct the history of these recombinations, we need to identify the positions where recombinations may have occurred, and develop algorithms to generate and explore the possible reconstructions.

Results: We first show that, provided that their gene order is co-linear, genomes of phages can be aligned, even if large parts of their sequences lack any detectable similarity and are annotated hypothetical proteins. We give such an alignment for 31 Staphylococcus aureus phage genomes, and algorithms that can be used in any similar context. These alignments provide the datasets needed for a combinatorial study of recombinations. We next reconstruct the most likely recombination history of the set of 31 phages, under the hypothesis that recombinations are partly homologous. This history relies on the computational identification of missing phages.

Conclusions: This first combinatorial study of modular recombinations acts as a proof of concept. We show that alignments of whole genomes are feasible for large sets of phages, and that this representation yields data that can be used to reconstruct parts of the evolutionary history of these organisms.

Figure 1

Phage recombination. Top: comparison of phages P and R along their sequence reveals an alternating pattern of highly similar and divergent regions. Bottom: a modular recombination event between phages P and R. It uses two pairs of highly similar regions of phages P and R to produce phage Q.

Figure 2

Alignment fragment. Fragment of an alignment of 31 Staphyloccocus aureus phage genomes that covers the segments between their terminase gene [module Te] and their tape measure gene [module Ta]. Module P is the anchor module corresponding to the portal gene. In a column, two cells that have the same color (or number) are highly similar. Empty sequences are designated by 0, and colored by their neighboring cells if both have the same color. Cells with variants that are unique are not colored.

Figure 3

The parents graph. The parents graph for the set of 31 phages. Vertices that are not incident to at least one edge are omitted. Vertices are labeled by phage name. The edge labeled F41, coming from phage F28 and going to phage F42, indicates that F42 can be produced by a recombination between F28 and F41.

Figure 4

A supergraph of the maximum recombination graph. The solid edges depict a maximum recombination graph for the set of 31 phages, augmented by the three missing parents M P0, M P1, and M P2. The graph corresponds to a recombination history with nine recombinations. Alternative recombinations represented by dashed lines can be substituted for solid lines to form other maximum recombinations graphs.

Figure 5

The missing parents graph. The clique in bold lines contains only templates, leading to missing parent 2 2 4 2 2 2.