Say what you want about the tone of the Graur et al. (2013) paper in Genome Biology and Evolution, but it has people talking. Including Ewan Birney, the lead scientist of the ENCODE project and the primary spokesperson for ENCODE in the media fiasco describing the “death of junk DNA”. Most recently, Birney was interviewed by Quentin Cooper on the BBC Radio 4 program Material World, along with Oxford biologist Chris Ponting. You can listen to the show here.
I have also transcribed the parts in which Birney discusses the ENCODE findings and the flap around the claims of “80% function” of the human genome. Again, remember that Birney himself said several times in prior interviews that the ENCODE results undermine the idea of junk DNA and that the genome is jam packed with “switches” (see here, here, here, and here).
Quentin Cooper (host): Ok, well, Ewan, we’ll get on to what this paper says and doesn’t say, but can you just give us a quick precis of why ENCODE’s findings are in such contrast to a lot of conventional thinking and clearly a lot of current thinking about junk DNA?
Ewan Birney (Lead scientist, ENCODE): I don’t think the findings are in such stark contrast. It’s more about the interpretation of the words, in particular when the words get used in, um, out of context, out of the scientific paper context and propagated. So, what exactly do we mean by this word “junk”?.
Quentin Cooper: But are you sure it’s all about the context. Because I mean, one of the reasons why these findings attracted so much interest was because it didn’t seem to fit the conventional thinking. It can’t just be down to a bit of phraseology and saying actually confirms what we already knew, can it?
Ewan Birney: Ah, so, I don’t — It’s interesting to reflect back on this. For me, the big important thing of ENCODE is that we found that a lot of the genome had some kind of biochemical activity. And we do describe that as “biochemical function”, but that word “function” in the phrase “biochemical function”is the thing which gets confusing. If we use the phrase “biochemical activity”, that’s precisely what we did, we find that the different parts of the genome, [??] 80% have some specific biochemical event we can attach to it. I was often asked whether that 80% goes to 100%, and that’s what I believe it will do. So, in other words, that number is much more about the coverage of what we’ve assayed over the entire genome. In the paper, we say quite clearly that the majority of the genome is not under negative selection, and we say that most of the elements are not under pan-mammalian selection. So that’s negative selection we can detect between lots of different
mammals. [??} really interesting question about what is precisely going on in the human population, but that’s — you know, I’m much closer to the instincts of this kind of 10% to 20% sort of range about what is under, sort of what evolution cares about under selection.
Quentin Cooper: But this paper that’s appeared in the journal Genome Biology and Evolution, Dan Graur from the University of Texas, professor there, all these lines, do you think they’re reacting more to the press coverage around the story rather than what’s actually in your paper itself?
Ewan Birney: That’s my belief. And of course in some sense our responsibility to help that press coverage do the right thing and that’s what I worked very hard in September, in particular in the UK context where I’m based, to try and make that press coverage work. It is quite complicated, because you want to be excited about what you’re doing, but you don’t want people to get the wrong — draw the wrong interpretation of it. So, it’s not an easy job to do, but I believe that most of the heat in this debate is about the definitions of the words, and not the data or the interpretation of the data.
Chris Ponting (Oxford University): Ewan, my question to you is, how much of the genome do you think is vital for life?
Ewan Birney: Yeah, I don’t, I would do that on a, as you know I’ve blogged about this. You know, certainly everything that’s under negative selection in the human population, that evolution cares about right now in humans, that if it changes then the person has less reproductive fitness, that’s clearly vital for life. I think there is a chance of there being a small amount of additional things that we find interesting about differences between people that are not under selection. So, those may be phenotypes that are late-onset such as neurodegenerative diseases or things like that. So, I think there’s a little addition to that but those are the kind of boundary components to that.
Chris Ponting: So I think we can probably agree between us that between 10% and say 20% is vital for life.
Ewan Birney: I mean, I think we would agree with that. I think, you know, refining that percentage down is quite interesting. I think also the other components that we — biochemical events that we see in the genome, sort of, each one of them are equally likely to be part of that 10% to 20% that we’re looking for. It’s important to realize that it’s not the case that we can spot the 10% to 20% just by looking harder. Each of these different places in the genome that have some biochemical activity associated with it, when there’s some phenotype screen that’s directed there or some evolutionary screen that’s directed to that point, ENCODE can now say “Ah ha! Here is a biochemical thing that this piece of DNA looks like it could be doing”.
Quentin Cooper: Ewan, just briefly, what about another aspect of the criticism, the idea that the ENCODE project lacked anyone with any real knowledge of evolutionary biology?
Ewan Birney: Well, I’m sure we could have, um, ahhh, had, um, many other people join us. There were a number of us who have worked — I do know quite a bit about evolutionary biology. Whether everybody considers me to be an expert, I don’t, you know, that’s for other people to say. If you read the paper, and not the press reports, there is a lot detail spent on what is under different aspects of evolutionary biology, ah, selection. So, I think again, a lot of this is not about the paper, but is more about the words used to describe the paper.
Quentin Cooper: Finally though, Ewan, is there any of the criticism you do take on the chin, think well perhaps we did let the story get a bit away from us at times?
Ewan Birney: Well, hindsight is a fairly cruel thing. And one of the things which I regret about being in this situation, arguing about words in the press, is I just wish there was a way of us not talking about this. I think ENCODE already is being used by many, many different groups, in particular disease biology groups having their phenotypes screened against it, and other people worldwide. And the whole point of this for the data by the project to be used by many, many other groups. I’m really happy about that, um, and hindsight being such a cruel thing, makes me think about what I could have done to minimize this kind of rather heated debate.