Guest Blog Post on Holobiont Theory by Jonathan Klassen and Sarah Kopac

Recently, Sarah Kopac and Jonathan Klassen described a new model to understand the evolution of host-microbe symbioses in their paper “Can They Make It on Their Own? Hosts, Microbes, and the Holobiont Niche”. In this model, hosts and microbes can change the shape of their respective niches, and thereby the context in which selection can act. This permits a test of holobiont theory by identifying instances where an organism’s phenotype depends on its symbiotic partners. Jonathan answered the following questions, incorporating feedback from Sarah. Be sure to read all the way through.

                    

1.     What motivated the theory reported in the paper?

It feels a bit murky now, but looking back I think there were three main motivations. First, we were quite struck by how host-microbe relationships can be thought of as a community ecology problem, i.e., where and how do interspecific relationships form and what is their outcome? So because much of the holobiont/hologenome literature has started from a population-genetics perspective (e.g., http://journal.frontiersin.org/article/10.3389/fmicb.2014.00046/full), we thought that drawing from a different intellectual tradition might be a way to get beyond current sticking points in the field's discussion. Another interesting aspect of the community ecology perspective is that it defines the context in which selection might act, leaving whether or not selection does act as a separate question. I think that it is too common to assume selection without rigorously testing against alternative hypotheses, e.g., drift or dispersal limitation, to our detriment. Second, we wanted to strongly highlight how any selection that did occur likely impacted hosts and microbes differently, e.g., because microbes have shorter lifespans and higher population sizes and dispersal rates than their hosts (http://doi.wiley.com/10.1002/bies.201500074). Third, one major take-away from my years of reading the lovely Dynamic Ecology blog (https://dynamicecology.wordpress.com/) is that mathematical models have a rigor and testability that verbal models cannot match, and thereby overcome the potential for verbal models to become misconstrued. Expressing our ideas mathematically so that they would be unambiguously testable therefore became an important goal.

2.     How did you come up with the title?

Truthfully, this was a revision suggested by one of the reviewers. (And they were right - thanks!) Sarah came up with this version, and I think it’s great because it really captures the key question of our model: do host-microbe interactions matter for the evolution of either partner? I think the answer is that it depends on the context, i.e., does the interaction change the shape of either partner’s niche in a way that changes how selection might act? I also love how (in my mind at least) there’s a U2 reference - https://www.youtube.com/watch?v=CuDqHtAR6L8. I’ve long been a fan.

3.     When and how did you two come together and agree on this paper? Were there varied opinions about how to approach the problem?

We agreed on the central idea of explaining holobionts in terms of niche theory early on, and so were unified on that front. There was a bit of divide and conquer after that, with Sarah focusing more on the examples of different niche shifts and I focusing more on the models themselves. Then we came back together and made sure that the examples we saw in the literature could be explained using our models. I found it very helpful to get someone else’s view of the literature – accurately synthesizing everything that’s out there alone would have been a massive challenge.

4.     What are the most salient findings?

I think that it is striking how our models are agnostic towards any particular mechanism of host-microbe interaction. For example, a similar shift in a host’s niche could be result from that host selecting microbes with a particular trait from the environment each generation, or it could be due to tight host-microbe co-evolution and vertical transmission. The important thing is that in either case the interaction changes the shape of a host’s niche in a way that selection might act upon. Both partners are therefore needed to completely describe host evolution. I am also struck by how our models accommodate the full diversity of symbiotic relationships, including the various forms of conflict that change the shape of a host’s niche but in a different way than mutualism. Finally, it seems that the symbiosis community has already been at least implicitly thinking in terms of our model because it was easy to find studies that had already tested it by changing one parameter at a time, e.g., by swapping microbiomes between constant host genotypes and vice versa. Hopefully our work can guide future experiments that continue to explicitly test these ideas.

5.     What are the most crucial questions moving forward in your mind? What do you want to do next? 

Perhaps one problem with our model is that precisely defining the shape of an organism’s niche is fiendishly difficult, mostly because there are a potentially infinite number of niche axes to consider. I think it will be interesting to understand how many of these are actually needed to come up with an accurate niche description. For example, to what extent to do microbe-microbe interactions need to be considered to describe how microbes alter a host’s niche? I also think it will be critical to learn more about microbes in non-host environments so that we can determine if hosts modify the niches of their microbial symbionts outside of obvious cases like intracellular mutualists and pathogens. Lastly and as described above, I think it will be crucial to explicitly test whether any host-microbe interaction phenotype actually arises due to selection, e.g., vs drift or dispersal limitation.

6.     Anything else you want to add?

Thanks to our colleagues in the symbiosis field for being so collegial, even in disagreement! I look forward to increasing the rigor of our studies, and to a deeper understanding of how ecology and evolution both shape host-microbe relationships.

My Talk and Interview on Microbes and Speciation from Germany

I returned last month from Kiel University for the 109th German Zoological Society Meeting. A Zoological Society Meeting alone is impressive these days, not to mention its 109 year history. Thomas Bosch invited me out for the keynote lecture. Thomas has been at the forefront of advancing a better appreciation of the natural world, namely the intricate interactions between a simple model system of the non-senescent cnidarian Hydra and its microbial community. Hydra represent an early key transition in the evolution of animals and therefore are critical to studying the origins of developmental mechanisms. Thomas is a CIFAR fellow and directs the Metaorganisms Collaborative Research Center, which is a beacon for systems biology thinking about the animal-microbiome assemblage.

Anyway, I presented our long-term studies on the role of bacteria in reproductive isolation and the origin of species. I presented old and new work, most recently by @ABrooksy19, @KevinDKohl, @liveinsymbiosis and @teddy1387 on phylosymbiosis across various animals. This work is currently in press.  Here's the talk and interview that the Collaborative Research Center clearly put a lot of work into - many thanks to the team.

 

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.