Saturday, October 15, 2016

Phage WO: Guest Blog Post by Sarah Bordenstein

The latest craze over phage WO, the bacterial virus that infects Wolbachia, has been both exciting and overwhelming. The press is great at communicating the science in a digestible format, but it can sometimes become sensationalized and misleading. When one press release builds upon the hype of a previous release, the end result is much like the game of telephone. As an author of “Eukaryotic association module in phage WO genomes from Wolbachia”, I want to make sure that the science in the public's eye is not over-represented and that we are providing a realistic view of the data.

Let’s first talk about what the paper is not, though headlines have claimed otherwise.
·      Phage WO does not encode the entire black widow venom (latrotoxin) gene. In fact, as we present in the paper, it contains DNA that is similar to just the C-terminal domain. This particular region of the gene is associated with the protoxin that is hypothesized to be involved in lysis of the spider’s secretion cells.
·      The phage did not necessarily “steal” the DNA from the spider. Yes, viruses hijack DNA from their hosts and this has been shown in both bacterial viruses and animal viruses. Viruses are incredible, rapidly evolving entities. Due to the level of divergence between the sequences in this particular study, the genetic transfer, if it did happen, occurred long, long ago. We can’t definitively say if the spider transferred to phage or phage to spider, but in our opinion both would be equally exciting. The current data leans towards spider to virus, possibly via a yet-to-be-discovered intermediary (see the paper for more discussion). We also can’t definitively say that it was even a legitimate transfer event. It could have been the result of convergent evolution. This is when different organisms independently evolve similar traits. Given the fact that widow spiders are often infected with Wolbachia, and Wolbachia are often infected with phage WO, there is an ecological niche that would provide opportunity for genetic transfer. Plus, we present other examples in the paper that support genetic transfer from animal to virus. Beyond that, many other research groups have reported the transfer of DNA between Wolbachia and their animal hosts, so the transfer between the phages and the animal is not a huge stretch.

With that said, this is what the paper is:
·      To our knowledge, this is the first report of animal-like DNA found in a bacterial virus. Is this a completely absurd, mind-blowing discovery? Not really. Bacterial viruses are known to exchange DNA with their bacterial hosts and animal viruses with animals. However, we don’t really know much about how viruses of bacteria might interact with animals. This field is really in its infancy.
·      Phage WO harbors a eukaryotic association module. About half of WO’s genome is devoted to structural genes (such as capsid, tail, baseplate) and other common phage elements. However, it also devotes a large percentage of its genome to unique genes that putatively encode functions relevant to animal interaction. Like some other viruses, phage WO appears to take different chunks of DNA from different sources and mix and match the chunks to create unique genes. What do these genes do? Do they retain the same functions as they did in the original donor? These are all still mysteries to be solved; so many questions left to be answered! I can tell you that some of the genes in the eukaryotic association module quickly grabbed our attention and we look forward to expanding the story of phage WO and Wolbachia in the months to come. Stay tuned…
·      Phage WO integrates into the Wolbachia genome via specific attachment (att) sites. Why does this matter? Wolbachia is an obligate intracellular endosymbiont. That means, it is dependent on its animal host for survival and cannot be cultured outside of the animal cell (as you would with standard free-living microbes such as E. coli). This makes it very hard for scientists to test functions of specific genes and fully understand its biology. We are particularly interested in Wolbachia because it infects over 40% of all arthropods as well as some nematodes of human health relevance and crustaceans. The identification of WO’s att sites offers a potential method of accessing the Wolbachia chromosome in order to unlock its secrets. Using the phage may or may not work, but it’s the best chance we have to-date. 
On a personal note, I want to thank journalists such as Ed Yong (The Atlantic - link) and Jacqueline Howard (CNN - link) for directly reaching out to us, the scientists, and making sure that they understood the complexity of the system rather than simply promoting catchy phrases. When it comes to science, words matter. I agree that this is a fun system to explore, but I hope that the science can stand on its own without adding falsehoods and making incorrect conclusions. 

Please don’t hesitate to reach out to scientists (including me) if you have questions about our research and possibly don’t believe or understand what you read in the news. We are honored to share this journey with you and are particularly delighted to hear from the next generation of researchers. Viruses are incredibly fascinating and, in my opinion, phage WO tops the charts. We are just beginning to explore the landscape of viruses infecting intracellular bacteria and I can’t wait to see what comes next.

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