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Genomic island variability facilitates Prochlorococcus–virus coexistence


Prochlorococcus cyanobacteria are extremely abundant in the oceans, as are the viruses that infect them. How hosts and viruses coexist in nature remains unclear, although the presence of both susceptible and resistant cells may allow this coexistence. Combined whole-genome sequencing and PCR screening technology now enables us to investigate the effect of resistance on genome evolution and the genomic mechanisms behind the long-term coexistence of Prochlorococcus and their viruses. Here we present a genome analysis of 77 substrains selected for resistance to ten viruses, revealing mutations primarily in non-conserved, horizontally transferred genes that localize to a single hypervariable genomic island. Mutations affected viral attachment to the cell surface and imposed a fitness cost to the host, manifested by significantly lower growth rates or a previously unknown mechanism of more rapid infection by other viruses. The mutant genes are generally uncommon in nature yet some carry polymorphisms matching those found experimentally. These data are empirical evidence indicating that viral-attachment genes are preferentially located in genomic islands and that viruses are a selective pressure enhancing the diversity of both island genes and island gene content. This diversity emerges as a genomic mechanism that reduces the effective host population size for infection by a given virus, thus facilitating long-term coexistence between viruses and their hosts in nature.

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Figure 1: Distribution of resistance-conferring mutations.
Figure 2: Phylogeny of representative MED4 mutant genes.
Figure 3: Attachment of podoviruses to resistant substrains.
Figure 4: Cost of resistance.
Figure 5: Resistance-conferring genes in the environment.

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The DNA polymerase and g20 sequences of the phages isolated in this study have been submitted to Genbank under the accession numbers JF837212 to JF837216.


  1. Partensky, F., Hess, W. R. & Vaulot, D. Prochlorococcus, a marine photosynthetic prokaryote of global significance. Microbiol. Mol. Biol. Rev. 63, 106–127 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Malmstrom, R. R. et al. Temporal dynamics of Prochlorococcus ecotypes in the Atlantic and Pacific oceans. ISME J. 4, 1252–1264 (2010)

    Article  Google Scholar 

  3. Zwirglmaier, K. et al. Basin scale distribution patterns of picocyanobacterial lineages in the Atlantic Ocean. Environ. Microbiol. 9, 1278–1290 (2007)

    Article  CAS  Google Scholar 

  4. Moore, L. R., Rocap, G. & Chisholm, S. W. Physiology and molecular phylogeny of coexisting Prochlorococcus ecotypes. Nature 393, 464–467 (1998)

    Article  ADS  CAS  Google Scholar 

  5. Bouman, H. A. et al. Oceanographic basis of the global surface distribution of Prochlorococcus ecotypes. Science 312, 918–921 (2006)

    Article  ADS  CAS  Google Scholar 

  6. Johnson, Z. I. et al. Niche partitioning among Prochlorococcus ecotypes along ocean-scale environmental gradients. Science 311, 1737–1740 (2006)

    Article  ADS  CAS  Google Scholar 

  7. Sullivan, M. B., Waterbury, J. B. & Chisholm, S. W. Cyanophages infecting the oceanic cyanobacterium Prochlorococcus . Nature 424, 1047–1051 (2003)

    Article  ADS  CAS  Google Scholar 

  8. Suttle, C. A. Viruses in the sea. Nature 437, 356–361 (2005)

    Article  ADS  CAS  Google Scholar 

  9. Thingstad, T. F. Elements of a theory for the mechanisms controlling abundance, diversity, and biogeochemical role of lytic bacterial viruses in aquatic ecosystems. Limnol. Oceanogr. 45, 1320–1328 (2000)

    Article  ADS  Google Scholar 

  10. Bohannan, B. J. M. & Lenski, R. E. Linking genetic change to community evolution: insights from studies of bacteria and bacteriophage. Ecol. Lett. 3, 362–377 (2000)

    Article  Google Scholar 

  11. Comeau, A. M. & Krisch, H. M. War is peace – dispatches from the bacterial and phage killing fields. Curr. Opin. Microbiol. 8, 488–494 (2005)

    Article  CAS  Google Scholar 

  12. Stern, A. & Sorek, R. The phage-host arms race: shaping the evolution of microbes. Bioessays 33, 43–51 (2011)

    Article  CAS  Google Scholar 

  13. Waterbury, J. B. & Valois, F. W. Resistance to co-occurring phages enables marine Synechococcus communities to coexist with cyanophages abundant in seawater. Appl. Environ. Microbiol. 59, 3393–3399 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Charlebois, R. L. & Doolittle, W. F. Computing prokaryotic gene ubiquity: rescuing the core from extinction. Genome Res. 14, 2469–2477 (2004)

    Article  CAS  Google Scholar 

  15. Dobrindt, U., Hochhut, B., Hentschel, U. & Hacker, J. Genomic islands in pathogenic and environmental microorganisms. Nature Rev. Microbiol. 2, 414–424 (2004)

    Article  CAS  Google Scholar 

  16. Hsiao, W. W. et al. Evidence of a large novel gene pool associated with prokaryotic genomic islands. PLoS Genet. 1, e62 (2005)

    Article  Google Scholar 

  17. Langille, M. G., Hsiao, W. W. & Brinkman, F. S. Detecting genomic islands using bioinformatics approaches. Nature Rev. Microbiol. 8, 373–382 (2010)

    Article  CAS  Google Scholar 

  18. Kettler, G. C. et al. Patterns and implications of gene gain and loss in the evolution of Prochlorococcus . PLoS Genet. 3, e231 (2007)

    Article  Google Scholar 

  19. Coleman, M. L. et al. Genomic islands and the ecology and evolution of Prochlorococcus . Science 311, 1768–1770 (2006)

    Article  ADS  CAS  Google Scholar 

  20. Dufresne, A. et al. Unraveling the genomic mosaic of a ubiquitous genus of marine cyanobacteria. Genome Biol. 9, R90 (2008)

    Article  Google Scholar 

  21. Palenik, B. et al. The genome of a motile marine Synechococcus . Nature 424, 1037–1042 (2003)

    Article  ADS  CAS  Google Scholar 

  22. Rodriguez-Valera, F. et al. Explaining microbial population genomics through phage predation. Nature Rev. Microbiol. 7, 828–836 (2009)

    Article  CAS  Google Scholar 

  23. Sullivan, M. B. et al. Genomic analysis of oceanic cyanobacterial myoviruses compared with T4-like myoviruses from diverse hosts and environments. Environ. Microbiol. 12, 3035–3056 (2010)

    Article  CAS  Google Scholar 

  24. Rocap, G. et al. Genome divergence in two Prochlorococcus ecotypes reflects oceanic niche differentiation. Nature 424, 1042–1047 (2003)

    Article  ADS  CAS  Google Scholar 

  25. Stoddard, L. I., Martiny, J. B. H. & Marston, M. F. Selection and characterization of cyanophage resistance in marine Synechococcus strains. Appl. Environ. Microbiol. 73, 5516–5522 (2007)

    Article  CAS  Google Scholar 

  26. Lenski, R. E. & Levin, B. R. Constraints on the coevolution of bacteria and virulent phage: a model, some experiments, and predictions for natural communities. Am. Nat. 125, 585–602 (1985)

    Article  Google Scholar 

  27. Luria, S. E. & Delbruck, M. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511 (1943)

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lythgoe, A. & Chao, L. Mechnisms of coexistence of a bacteria and a bacteriophage in a spatially homogeneous environment. Ecol. Lett. 6, 326–334 (2003)

    Article  Google Scholar 

  29. Somova, A. G. Frequency of phage-resistant mutations and effect of the bacteriophage on the formation of resistant forms of Vibrio cholera . Bull. Exp. Biol. Med. 31, 99–103 (1966)

    CAS  Google Scholar 

  30. Rusch, D. B. et al. The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. PLoS Biol. 5, e77 (2007)

    Article  Google Scholar 

  31. Yooseph, S. et al. The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families. PLoS Biol. 5, e16 (2007)

    Article  Google Scholar 

  32. Parsons, Y. N. et al. Suppression-subtractive hybridisation reveals variations in gene distribution amongst the Burkholderia cepacia complex, including the presence in some strains of a genomic island containing putative polysaccharide production genes. Arch. Microbiol. 179, 214–223 (2003)

    Article  CAS  Google Scholar 

  33. Walker, C. B. et al. Contribution of mobile genetic elements to Desulfovibrio vulgaris genome plasticity. Environ. Microbiol. 11, 2244–2252 (2009)

    Article  CAS  Google Scholar 

  34. Fuhrman, J. A. et al. Annually reoccurring bacterial communities are predictable from ocean conditions. Proc. Natl Acad. Sci. USA 103, 13104–13109 (2006)

    Article  ADS  CAS  Google Scholar 

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We thank E. Zinser for the bacterial helper strain; I. Pekarsky for help with adsorption assays; I. Izhaki for advice on statistical analyses; O. Beja, Y. Mandel-Gutfreund, K. Kozek, U. Qimron and Lindell lab members for comments on the manuscript; and T. Dagan for coining the term ‘susceptibility region’. Genome sequencing was carried out at the genome sequencing units at the Weizmann Institute of Science and the Technion – Israel Institute of Technology. This work was supported by a European Commission ERC Starting Grant (no. 203406), an ISF Morasha grant (no. 1504/06) and the Technion Russell Berrie Nanotechnology Institute (D.L.); and by an ISF-FIRST grant (no. 1615/09) and an ERC Starting Grant (R.S.). O.W. was supported by an Azrieli fellowship and D.L. is a Shillman fellow.

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S.A. and D.L. designed the project and the experiments; S.A. performed and analysed the laboratory experiments, PCR screening and phylogenetic analyses; O.W. performed the bioinformatic analyses and, together with R.S., analysed the genome sequencing data; I.S. analysed the environmental sequences; and D.L. wrote the manuscript with significant contributions from all authors.

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Correspondence to Debbie Lindell.

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The authors declare no competing financial interests.

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Avrani, S., Wurtzel, O., Sharon, I. et al. Genomic island variability facilitates Prochlorococcus–virus coexistence. Nature 474, 604–608 (2011).

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