Comparative Genomic Analysis of 60 Mycobacteriophage Genomes: Genome Clustering, Gene Acquisition, and Gene Size

Abstract

Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of sixty -all infecting a common bacterial host -provides further insight into their diversity and evolution. Of the sixty phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, five of which can be further divided into subclusters; five genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the six genomes in cluster D share more than 97.5% average nucleotide similarity with each other. In contrast, similarity between the two genomes in Cluster I is barely detectable by diagonal plot analysis. The total of 6,858 predicted ORFs have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit smaller average size than genes of their host (205 residues compared to 315), phage genes in higher flux average only ∼100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains.

The First Structure of a Mycobacteriophage, the Mycobacterium abscessus subsp. bolletii Phage Araucaria

“…Using the Pfam database, an integrase domain was detected toward the C terminus of this ORF protein, between amino acid positions 67 and 241 (Pfam: PF0058). Temperate mycobacteriophages typically encode either a serine or tyrosine integrase that mediates prophage integration (8)(9)(10)(11)13). In the Araucaria prophage genome, the ORF2 protein is perfectly identified as a tyrosine integrase and is located 22 kb distant from the cluster of structural proteins (Fig.…”

“…This large set of complete genomes reveals a considerable diversity (8)(9)(10)(11). Conversely, the large genetic repertoire of the predicted mycobacteriophage protein-coding genes possesses a low number of detectable homologues in the public databases (9,10).…”

“…Besides the interest in phages infecting a bacterial pathogen, studies of mycobacteriophages may reveal specific features of mycobacterium-phage interactions due to the peculiar cell wall features of these hosts (12). Despite the wealth of mycobacteriophages isolated and sequenced (8)(9)(10)(11)13), their infection and host recognition mechanisms are still poorly understood.…”

A wavelet-based feature vector model for DNA clustering

“…Leimeister and Morgenstern (2014) compared DNA sequences based on the longest common substrings with k mismatches. Eisen (1998), Yi et al (2007), and Hatfull et al (2010) clustered genomes by various types of statistical information from DNA microarray data. Bonham-Carter et al (2014) summarized 14 alignment-free genetic sequence comparison methods.…”

Phage on the stage

“…Large-scale comparative genomics of these mycobacteriophages have emerged and have been published with dozens of faculty and student authors. 31,32 Faculty involved in the SEA-PHAGES program are developing other host organisms (such as Arthrobacter, Bacillus, Paenibacillus, and Rhodococcus) for bacteriophage isolation in this educational setting and are collecting multiple phages using these hosts. One large and 2 small-scale comparison papers have already been published on the Bacillus phages.…”