Causes and consequences of bacteriophage diversification via genetic exchanges across lifestyles and bacterial taxa

Abstract

11 12Bacteriophages (henceforth phages) evolve by mutation and recombination. Temperate 13 phages are known to evolve rapidly by genetic exchanges. In contrast, recombination events 14 between virulent and between temperate and virulent phages have rarely been reported. A 15 gene flow barrier between these two large distinct groups of phages could affect the ability of 16 phages to acquire novel functions. Here, we show that genomes of temperate and virulent 17 phages are very distinct but often have a few almost identical genes. These cases are due to 18 recent genetic exchanges of both phage-like and bacterial-like genes. These exchanges were 19 probably mediated by phage recombinases with low homology requirements and mechanisms 20 of non-homologous end joining, since both were over-represented in recombinant phages and 21 their hosts. When assessing the impact of gene flow across the two populations of phages we 22 realized that temperate phages have narrower host ranges than virulent phages. This 23 suggests, and we find some evidence, that gene flow between temperate phages infecting 24 distant bacterial hosts might be mediated by recombination with the broader host virulent 25 phages. Hence, gene flow across phages with distinct lifestyles could drastically increase the 26 gene repertoire available for phage evolution, including the transfer of functional innovations 27 across taxa. These results also have implications for bacterial evolution because of the impact 28 of phage predation in bacterial population dynamics and the contribution of temperate phages 29 to the evolution of bacterial gene repertoires. 31 SIGNIFICANCE STATEMENT 33Many microbial communities are intensely predated by temperate and virulent 34 bacteriophages. The former also contribute to bacterial gene repertoires. Gene transfers 35 between bacteriophages favor their rapid adaptation, but are thought to occur rarely between 36 virulent and temperate bacteriophages because their genomes are very different in terms of 37 gene repertoires and genetic organization. We found that genetic exchanges occur frequently 38 3 between these types of bacteriophages, involve different phage and bacterial functions, and 39 are likely due to multiple DNA repair processes. Since we show that virulent bacteriophages 40 have broader host ranges, they can shuttle genes between temperate bacteriophages present 41 in taxa that are beyond the typical range of the latter. This enhances phages diversification 42 and has multiple impacts on bacterial evolution. 43 65 accretion in virulent phages, even if some families of virulent phages have remarkable 66 diversity in their genomes' size, suggesting the existence of mechanisms of gene exchange 67 (12). The genomic plasticity of temperate lambdoid phages has been much more extensively 68 studied (9, 13, 14). Their analyses reveal that pairs of phages tend to have patches of regions 69 of very similar sequences within genomes that are often very dissimilar. This genome 70 mosaicism is facilitated by the modular or...

Systematic and quantitative view of the antiviral arsenal of prokaryotes

“…To do so, we detected prophages in the genomes of our database using Virsorter2 28 (see methods). We found 51 582 prophages in 16 315 genomes, with on average two prophages per genome (Supplementary Figure 3) which is in line with previous detection 29 . The number of prophages correlates both with the number of systems (Spearman ρ=0.10, p-value<0.0001) and the number of families (Spearman ρ=0.25, p-value<0.000).…”

Taxonomy-aware, sequence similarity ranking reliably predicts phage-host relationships

“…Proteins rich in phage-host BLAST alignments can be assigned into different functional categories including phage virion components, replication-related proteins, regulatory factors, and proteins involved in the metabolism of the host. The transfer of some over-represented families in phages and/or prophages has been previously reported (e.g., lytic proteins, DNA replication and recombination proteins, and enzymes involved in nucleotide and energy metabolisms [36]) and some of these genes are connected with the phage-host range [37, 38]. However, no clear pattern emerges after analyzing the functions of the remaining, over-represented proteins.…”

BACPHLIP: Predicting bacteriophage lifestyle from conserved protein domains

“…We unite these ideas in one framework and show that doing so leads to large improvements in the ability to predict whether a given phage is temperate or virulent. Critically, BACPHLIP rapidly creates predictions from un-annotated genome sequences alone, and thus can facilitate large-scale studies into phage genome evolution (Moura de Sousa et al, 2021). Given the rapid expansion of phage genome data sets (Roux et al, 2021;Camarillo-Guerrero et al, 2021), comparative genomic analyses have the potential to drastically increase our understanding of phage diversity and function.…”

“…Additionally, some mobile genetic elements blur the lines between temperate phages and plasmids, subverting our basic classification systems (Pfeifer et al, 2021). Nevertheless lifestyle classification into temperate and virulent categories is broadly recognized and important in numerous contexts (Mavrich and Hatfull, 2017;Moura de Sousa et al, 2021).…”