Viruses more than meets the eye

This study aims to understand the mechanisms for the coexistence between Prochlorococcus sp. and its viruses by using whole genome sequencing and PCR screening. Hosts and viruses must coexist in nature, and a paradox exists in that viral infection generally causes death of a cell, which therefore provides selection pressure for viral resistance. Conversely, the viruses need susceptible cells to infect and facilitate replication. Their coexistence is a source of much debate. The evolutionary arms race is the most popular theory, which is competition between two sets of genes that develop adaptions and counter adaptions to each other, resembling a positive feedback loop (Gallup and Burch, 2016).

A large contributor to primary production, Prochlorococcus sp. is a cyanobacteria that has two types of high light adapted ecotypes: HLI and HLII. They exist in large but distinct ranges and are both infected by prodoviruses and myoviruses, which are common in the ocean. As Prochlorococcus sp. coexists with its viruses, this suggests there must be a small number of non-resistant cells to ensure viral replication. Data from the study suggests that there are both resistant and susceptible subpopulations in the wild.

The study isolated resistant sub-strains, finding 12 mutants that are resistant to infection. These were sequenced and screened from genetically similar populations. A genomic island is a region of the genes that show evidence of horizontal origin (Langille et al., 2010). The study found that these mutants had stable core genes that were dotted with genomic islands. All resistant mutant genes were found within these hypervariable genomic islands. Most of the mutants had a single mutant gene, but there were cases of multiple mutations within the genomic island.

The genomic islands are important as the nature of horizontal transfer injects variation into the species. Most of the genes enabling resistance occurred in a single genomic island. The study suggests that these genes were acquired horizontally from bacteria. There was evidence of horizontal swapping of genes between different Prochlorococcus sp. strains. This is interesting as it seems to suggest that the genomic island exists as a pool of resistance. These are moved around the population as needed, preventing total extinction of the species. Although these mutant genes are rare in nature, some of these phenotypes have been found experimentally.  

The mutations that conferred the resistance where found to exist in five different genes. The majority are associated with the cell membrane or cell wall. The resistance is caused through alterations to the cell surface, which was confirmed by testing viral attachment to resistant cells. The mechanism of the resistance could be the mutations altering cellular receptors, preventing the virus from binding. This is a common method of resistance to lytic phages in bacteria and could be further evidence that some genes in the genomic island were acquired originally from bacteria. Podoviruses attach to specific cell surface components that change depending on the strain of virus. Therefore, the range of viruses a population is resistant to is dependent on the diversity of the genomic islands as the virus has specificity regarding the host it affects.

For the virus to exist, there must be some cost to resistance as all susceptible individuals would be selected against. When assessing the growth in resistant populations, it was found they grew 50% slower. Also, it was discovered that resistance to one virus led to increased susceptibility to another. The study found 16 out of 23 mutants either grew slower or were more susceptible to other viruses; however, despite these costs the resistant strains are not out competed.

The diversity of the genomic island determines the range of viral resistance. Interestingly, the study suggests the composition of the genomic islands is driven by the viral selective pressure. The resistance to a virus did not occur in the same gene in each strain, which could mean that resistance is dynamically gained and lost in response to viral selection pressure. It is thought that this selection pressure is due to millions of infection-selection cycles, rejecting proteins that aid viral attachment. The dynamic nature of the horizontal gene transfer found in the genomic islands allows for gene exchange while maintaining the rest of the genomes integrity.  The distribution of the genomic islands throughout the population has allowed some degree of resistance to multiple phages and has created subpopulations with different susceptibilities.

An implication of this is the possibility that there is a micro diversity in Prochlorococcus sp., which is driven by the viruses themselves through selection pressure and horizontal gene transfer. This provides an assortment of interchangeable genes that provide viral resistance, creating a robust population. It could be concluded that this could be true for other bacteria through the numerical refuge hypothesis: small subpopulations that are susceptible to any one phage keep the total population relatively free from disease. Also, this provides the virus with enough hosts to exist and be a driver of genetic diversity, suggesting that viruses have implications on a evolutionary scale and not just as a means of disrupting trophic flow.

References

Gallup, G.G. and Burch, R., 2016. Evolutionary Arms Race. Encyclopedia of Evolutionary Psychological Science, pp.1-2.

Langille, M.G., Hsiao, W.W. and Brinkman, F.S., 2010. Detecting genomic islands using bioinformatics approaches. Nature Reviews Microbiology, 8(5), pp.373-382.

Article Reviewed

Avrani, S., Wurtzel, O., Sharon, I., Sorek, R. and Lindell, D., 2011. Genomic island variability facilitates Prochlorococcus-virus coexistence. Nature, 474(7353), pp.604-608.