I've been inspired by a couple of recent twitter conversations I've had to write a post and basically lay out why using the phrase "ecological epistasis" triggers my population genetics spidey-sense.
The first conversation happened about a month ago while I was sitting through previews for the completely satisfying movie Pacific Rim.
Epistasis between the nuclear genome and #microbiome underscores the #hologenome Not a far fetched idea and soon to be non-controversial.The second happened yesterday (Ian is live tweeting a bunch of talks at BEACON and Maren Freisen (@symbiomics) was talking about her Medicago research)
— Seth Bordenstein (@Symbionticism) July 14, 2013
Friesen: Although she phrased it as ecological epistasis. #2013beacon.I'm using this space as a way to crystallize my thoughts and to try and solicit other opinions. I'm also going to try and be involved in Seth Bordenstein's G+ chat on the hologenome in a couple of weeks, so consider this a bit of a warmup.
— Ian Dworkin (@IanDworkin) August 14, 2013
Epistasis is a tricky word. Problems arise when different (yet highly related and somewhat overlapping) groups start to use the same word yet mean different things. One of the people responsible for making me the scientist I am today has written on this topic (here and here), so I won't go too much into it. To summarize though, you can define epistasis in the quantitative genetics sense (multiple loci interacting in a non-additive way), in the small genetic sense (two proteins actually interact or function in the same pathway as would be found by genetic screen) or you can define it in the larger genetic sense (interactions between multiple genes). Neither is wrong per se, but use of the same term can get confusing depending on your audience. I don't have a problem with any of these definitions, but I just think that making headway in biology always becomes more difficult when you have to start referencing quotes from Justice Potter Stewart.
So here's a couple of my problems with "ecological epistasis". This uses the latter definition of the term that I mention above, gene interactions writ large. If you have two co-evolving organisms, genes from one organism interact with genes from the other organism in the population genetics sense, fitness of one organism is dependent on the other organism, all well and good (if I'm misinterpreting, please let me know). We already have language to describe these circumstances though, in terms of Gene by Environment (GxE) interactions without the need to invoke the "e" word. In this case each organism is the co-evolving organisms environment variable. Why not modify this term a little bit and call it GxEG (environment/genetic) interactions? There is nuance in this specificity that isn't captured by using the term epistasis. This isn't really my area of expertise, but I'm guessing that dynamics that apply to interactions between genes residing in different genomes may be inherently different than those in linked together and vertically inherited.
The second idea that needs clarifying IMHO is what the limits on interactions between organisms are when speaking in population genetic terms. When I've seen the phrase "ecological epistasis" used, it's in reference to interactions between intimately co-evolving organisms. However, if you are going to define the term as interactions between genes in different organisms without specificity, you could extend the definition in absurdum. Much of my work focuses on plant pathogenic bacteria, and genomes of both the host and pathogen encode for proteins that mediate interactions between the two. Is this "ecological epistasis"? Stepping further back, this morning I killed a cricket that tormented my household last night (keeping my 8 month pregnant wife awake more than usual...I have no regrets about my actions). In result this is no different than a pathogen killing a host, just that co-evolutionary interactions are weaker between me and the cricket population at large than in typical pathogen/host dynamics. My foe and I both have genomes that encode for proteins that ultimately mediated our interactions this morning. Is this "ecological epistasis"? Ian Ziering managed to fight off a shark with a chainsaw:
I'll save my hologenome critiques (great term, needs limits on the definition) for a future blog/G+ chat. My point is simply that if you start defining interactions between organisms, that these interactions can take a wide variety of forms that you may not inherently consider. Specific wording could avoid me having to make sharknado references.
It's not that I think that using "epistasis" in the context of interacting organisms is improper. I think that the term is muddled enough as is that it doesn't make sense to use it for the sake of linking onto an already established (and muddled) term. Using "ecological epistasis" doesn't clarify things in the way that a more nuanced term could, at least to me, but maybe I'm just missing something?
Update: Maren Friesen has clarified what she was referencing in her talk:
ecological epistasis!=GxE; it's non-additive effects of spp on ecosystem @Symbionticism @surt_lab @IanDworkin @Graham_Coop @liveinsymbiosis
— ML Friesen (@symbiomics) August 16, 2013
So...4) non-additive interactions between species (not genes)
Update 2: Great response by Maren Friesen
Nice post and way to drum up interest in this important area. Patrick Phillips' 2008 paper that you referenced above has some interesting features. I sense that he cant even come to a decision on what epistasis should mean :-) but correct me if Im wrong. In particular I highlight two quotes.
ReplyDeleteFirst, from his interpretation of Bateson's, he states
"It was clear from these circumstances that the mutations must be interacting with one another, at least in the loose sense that they exist within pathways that both influence the same phenotype"
Here I would assert that beneficial microbes and the host genome interact to influence the same phenotype. Hence, we end up where we started with Bateson's original definition. Epistasis underscores host-microbe interactions and thus the hologenome.
His last sentence in the paper is full of foresight that reflects the emergence of system biology terms.
"Given recent work in this area, it is likely that for the next 100 years the concept of epistasis will be even more central to biology than it has over the last 100"
I also like your call for refining out the confusion around the hologenome.
"However, if you are going to define the term as interactions between genes in different organisms without specificity, you could extend the definition in absurdum"
The hologenome really does not extend to everything microbial in a host, but probably to the compartments of the microbiome that are beneficial if not essential to Life.
More to follow in a blog or google+ hangout (https://plus.google.com/u/0/events/c2lnc32smhslqf9nddh3l6crdj0).
To quote PPhil yesterday: "actually I proposed getting rid of "epistasis" for the pop gen usage as Ian suggests in 1998. No takers."
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