A Selective Barrier to Horizontal Gene Transfer in the T4-Type Bacteriophages That Has Preserved a Core Genome with the Viral Replication and Structural Genes

Abstract

Genomic analysis of bacteriophages frequently reveals a mosaic structure made up from modules that come from disparate sources. This fact has led to the general acceptance of the notion that rampant and promiscuous lateral gene transfer (LGT) plays a critical role in phage evolution. However, recent sequencing of a series of the T4-type phages has revealed that these large and complex genomes all share 2 substantial syntenous blocks of genes encoding the replication and virion structural genes. To analyze the pattern of inheritance of this core T4 genome, we compared the complete genome sequences of 16 T4-type phages. We identified a set of 24 genes present in all these T4-type genomes. Somewhat surprisingly, only one of these genes, that encodes for ribonucleotide reductase (NrdA), displayed evidence of LGT with the bacterial host. We test the congruence of the inheritance of the other 23 markers using heat map analyses and comparison of a reference topology with the 23 individual gene phylogenies. The vast majority of these core genes share a common evolutionary history. In contrast, analyses of all the noncore genes present in the same 16 genomes, located in the hyperplastic regions of the genome, show considerable evidence of frequent LGT. The similar evolution of the core replication and virion structural genes in the T4-type phage genomes suggests that, unlike the situation in many other phage groups, such portions of T4-type genome have been inherited as a block, without significant LGT, from a distant common ancestor. The preservation of the synteny of the core T4 genome could result from several factors acting in synergy, such as the constraints imposed by the sophisticated regulation of the transcription. Moreover, numerous and complex protein-protein interactions during virion morphogenesis could also impose a supplementary barrier against LGT. Finally, there may be some real evolutionary advantage to maintaining large regions of conserved sequence. Such segments could be a sort of genetic glue that maintains the genetic cohesion of the T4-type phages via recombination within the most conserved sequences. This could mediate the swapping of nonconserved sequences that they flank.