Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

Abstract

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery.DOI: http://dx.doi.org/10.7554/eLife.06416.001

Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses

“…These included viral genomes not yet added to RefSeq, as well as genome fragments from fosmid libraries generated from seawater samples 12,13 . Mycophage sequences (available from http://phagesdb.org 62 ) and not already in RefSeq were downloaded (July 2015) and included as well (734 sequences). Finally, 12,498 viral genome fragments from the VirSorter Curated Dataset, identified in publicly available microbial genome sequencing projects, were added to the database 9 .…”

Testing hypotheses for the presence of tRNA genes in mycobacteriophage genomes

“…For example, phage genomes may contain genes for DNA polymerase and/or helicase. 2,6 The products of some phage genes modify the bacterial RNA polymerases to increase transcription of early phage genes. [7][8] In addition, phages can encode their own tRNA genes, and the occasional presence of the tRNA genes has been called intriguing.…”

“…13 The existence of a large database of mycobacteriophages that have been mostly isolated on a common host, Mycobacterium smegmatis (strain mc 2 155; GC content 67.4%) provides an opportunity to examine the presence/absence of tRNA genes within a comparative context. 6 These phages belong to 2 families, the siphoviridae and the myoviridae. Further, they can be grouped into different clusters based on genetic similarity, with different methodologies (e.g., average nucleotide identity, gene content analyses) providing concordant clustering.…”

Innovations in Undergraduate Science Education: Going Viral

“…This is by far the largest collection of sequenced phage genomes for any single bacterial host strain and represents about a third of all sequenced double-stranded DNA phage genomes. Even though all these are in principle in direct genetic contact with each other, the population is highly diverse, with many different types of genomes, albeit with mosaic architectures (9,10). This wealth of new genetic information has contributed to numerous peer-reviewed publications, underscoring the authenticity of the research advances.…”

“…This wealth of new genetic information has contributed to numerous peer-reviewed publications, underscoring the authenticity of the research advances. Because phage genomes are relatively small and cheap to sequence, the availability of phage isolates becomes a limiting factor, and the SEA-PHAGES program resolves this bottleneck (9). The program also promotes advances in student learning gains and retention in STEM disciplines (8), as well as heightened engagement as seen through networking analyses (20).…”