Megaphages infect Prevotella and variants are widespread in gut microbiomes - PubMed (original) (raw)

doi: 10.1038/s41564-018-0338-9. Epub 2019 Jan 28.

Joanne M Santini 2, Matthew R Olm 3, Karthik Anantharaman 1 4, Patrick Munk 5, Jenny Tung 6, Elizabeth A Archie 7, Peter J Turnbaugh 8 9, Kimberley D Seed 3 9, Ran Blekhman 10, Frank M Aarestrup 5, Brian C Thomas 1, Jillian F Banfield 11 12 13

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Megaphages infect Prevotella and variants are widespread in gut microbiomes

Audra E Devoto et al. Nat Microbiol. 2019 Apr.

Abstract

Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.

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Conflict of interest statement

J.F.B. and B.C.T. are founders of Metagenomi. A.E.D. is an employee of Metagenomi as of 1 September 2018.

Figures

Fig. 1

Fig. 1. Alignment of the CRISPR arrays on four Prevotella scaffolds containing repeat GGTTTAATCGTACCTTTATGGAATTGAAAT.

The green rods indicate repeats, the coloured rods indicate spacers. The same colour indicates the same spacer sequence, except for black rods, which indicate spacers different between individuals 26 and 28 (probably added to the diversifying locus ends). The red arrows indicate spacers targeting megaphages (also see Supplementary Fig. 3).

Fig. 2

Fig. 2. Genomic features and variation in Lak phage genomes.

a, Frequency of use of the TAG repurposed stop codon overlying the alignment of the A1 and A2 genomes. The red bars indicate regions >5 kb without TAG codon use. Structural proteins (dark blue) are mostly encoded in regions with high TAG use. CDS, coding sequence. The boxed region is shown in detail in b. b, Alignments of each distinct Lak phage genome against the A1 genome. A subset of this region was used in the pig Lak phage genome fragment alignments (Supplementary Fig. 6).

Fig. 3

Fig. 3. Comparison of B-Lak phage genomes reveals identical sequence blocks in a subset of the B-Lak phage.

a, Sequence variation in a ~20 kb region of the aligned B-Lak phage genomes with B1 as the reference. The coloured bars underline blocks with a shared sequence. Note evidence of admixture of sequence blocks, indicative of extensive homologous recombination among phages sampled from individual baboons. For the full alignment of the nine complete B-Lak phage genomes, see Supplementary Fig. 13. The box indicates the B9 region examined in detail (Supplementary Fig. 14). b, Relatively conserved and divergent regions in A1, A2 and C1. The open box indicates the region shown in a.

Fig. 4

Fig. 4. Alignment of sequences with a possible tRNA Thr (TGT).

Some tRNAs are predicted to contain an intron that itself may encode a tRNA (dashed box with superimposed secondary structure). With the exception of the Hadza sequence, all introns are identical.

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