Interviewer: Dr. Green, can we start with you? Would you
give us a brief overview of the vision of this general initiative in, you know, to obtain
the whole genome sequences of more than 10,000 vertebrae species? What’s this about?
Dr. Green: So, what it’s about is really trying to
bring genomics to the study of evolutionary biologists. The fact is evolutionary studies
done by evolutionary biologists or naturalists or paleontologists have for years mostly focused
on morphological features -- in some cases maybe physiological features of organisms
-- and tried to trace the evolutionary relationships. What contemporary genomics has taught us is
that the information that has been driving evolutionary processes are all coded in the
genomes of all these living organisms. And as we have learned how to explore genomes
by mapping them and more recently sequencing them, it has given us great insights about
evolution. The idea of this project is to basically start to open up evolution’s notebooks
by actually sequencing the genomes of many, many species in an attempt to provide a new
way of doing evolutionary type studies using genomics.
Interviewer: Dr. Felsenfeld, we’ve been -- the National
Human Genome Research Institute has been doing model organism research for some time. Could
you tell us a little bit about what we’ve been doing and how this would fit into that?
Dr. Felsenfeld: The National Human Genome Research Institute
has been very interested in particular organisms, the sequences of particular organisms, for
mostly -- for biomedical research reasons. So, the easiest to -- the sort of first that
we look at are organisms that are used extensively in biomedical research: for example, mouse
and there are others. In addition, there are questions that are more general and biologically
more general -- to provide more general biological insight. As Eric mentioned, to be able to
compare genomes between species; by that comparison, you can find regions of the genome that are
conserved and you can make inferences about their function.
Interviewer: Dr. Green, this project seems fairly ambitious.
This is a large number of species that you’re interested in doing that. What makes it possible
to do this now? Is there some change in technology, cost structure?
Dr. Green: Let’s set a context. So, so far we’ve
as a community sequenced maybe something on the order of 30 to 40 vertebrae genomes if
we just focus on vertebrates, which is pretty much what this initiative is all about. And
those have been selected because they’ve had the closest relationship to the kinds
of things that the National Institutes of Health in particular would be interested in,
but that’s just barely opening up the window of opportunity for these types of genomic
studies. We can imagine a day where the kinds of questions that you’d really want to ask
to trace the evolutionary origins of all types of biological innovations across the vertebrate
phylogenetic tree would require many more species’ genomes to be sequenced. What has
occurred in the last five years have been some spectacular advances in DNA sequencing
technologies that are rapidly driving down the cost of sequencing a new genome. It turns
out that for these studies, and ironically even the first 30 to 40 genomes that we’ve
sequences of other vertebrates, that what can be very rate limiting is picking the species,
getting the DNA and making sure you know something about the exact species that you picked and
certain details about it, and so forth. And if it was limiting for the first 30 to 40,
when you start thinking about getting the DNA in hand ready to go for thousands, it
was recognized that we should start now.
Interviewer: And Dr. Felsenfeld, help to set the context
a little bit more so -- because we’re not actually talking about sequencing right now.
What we’re actually -- what’s an idea that you guys are kicking around?
Dr. Felsenfeld: When a lot of people -- when a few people
were doing sequencing and sequencing was very expensive, it was relatively easy to coordinate.
When there are now going to be many people who are able to turn out a high quality genome
sequence, coordination has to be accomplished if only to avoid duplication in effort. Even
if it’s cheap, it’s going to be useful to avoid duplication of effort. In addition,
there are all the benefits of understanding data quality; understanding sample quality
so people don’t have to fiddle around with the samples too much before they start to
sequence, to come into agreements about depositing the data so that everybody can work on the
data as a community, and all those things that were served by having sequencing done
previously in just a few centers can also be served by having well-organized front end,
if you like, to a very large sequencing effort.
Interviewer: Let me sort of clarify that. You guys are
not -- NHGRI is not watching this project and this is not something that we’re automatically
doing. You’re both sitting here because you’re coauthors of a paper about the idea
of doing this, and that you’re part of the scientific community, and this is a discussion
about how this might go forward. And you raise a really interesting question about how this
would be organized. How would this be organized?
Dr. Green: This paper is coming out of a workshop that
a set of colleagues in the field -- they’re not even all genomics people. We’re also
including a zoologist, and someone who studies conservation, biology or conservation.
Dr. Felsenfeld: Mostly not genomics.
Dr. Green: Mostly not genomics people. They convened
a meeting of folks that included sort of genomics geeks like us, that included some computational
biologists and evolutionary biologists; a whole very diverse, multi-disciplinary group,
all who recognize that wouldn’t it be cool if 10 or 20 years from now you could go to
the internet and access genome sequences of 10,000 to 15,000 vertebrates. This would create
a whole new way of doing evolutionary studies. They realized to get that going, you’ve
got to get organized, but you also need sort of an interdisciplinary team to be thinking
about it. This was the first organizational meeting for this initiative and coming out
of it was a plan to move forward to start to identify the species, collect the DNA,
get it ready for the sequencers.
Interviewer: Is there a vision of what that organization
might look like?
Dr. Felsenfeld: At one extreme you could imagine this eventually
being done as a centralized effort that whips out 10,000 or more genomes. I don’t actually
think it’s going to look like that. What I think it’s going to be is the actual sequencing
is eventually going to be more dispersed. And I think there’s a really good reason
to do that. First of all, people will be able -- because the technology changed, people
will be able to do that. And I think it brings many more people into the community of those
who really think hard about these data, and it will ultimately result in more different
kinds of insights coming from the same data.
Dr. Green: Although initially it might be that it’s
centralized at the organizational level; maybe even collecting the DNA, making the repository,
trying to get some consistent quality and so forth and then maybe dispersed out for
the actual sequencing. Or a little -- there can be a mixed model.
Interviewer: How much will something like this cost to
do it? I mean, and what will be the funding mechanisms to support this kind of effort?
Dr. Felsenfeld: I think it’s premature to talk about -- if
by “this effort” you mean the actual sequencing, I think it’s premature to talk about. I
think the organizational steps are actually probably not going to be expensive because
they’ll take a person or two to -- and some computational facility -- to organize everything
into a collection that people can look at, and a lot of leg work in coordinating with
those individuals who actually have done the hard work already of collecting these samples
and will hopefully be doing ongoing work in collecting more samples in the routine course
of doing their research.
Interviewer: How long will something like this take?
Dr. Green: Unclear -- the whole thing, it’s unclear
in part because we don’t precisely know what the curve will look like for DNA sequencing
costs and issues like that. We don’t totally know where the money’s going to come from
to completely do it. But in terms of getting out of the gates and making decisions -- I
mean there’s preliminary decisions that have already been made. I described in the
paper about what species to start thinking about. Some people already have the DNAs in
hand and now can start to contribute them to a central collection and there are possibilities
of people now moving forward and collecting additional -- getting in hand additional DNAs
to contribute to this. So I think it’s already starting, and I think it’s realistic to
imagine that a good collection of these DNAs could happen in a small number of years.
Interviewer: How many species are we talking about here?
Dr. Felsenfeld: Well in the paper they’re proposing 16,000
total. That’s a pretty good representation of the 60,000, roughly 60,000 known vertebrate
species.
Interviewer: What would Darwin have said if he could see
the notebooks that you guys are about to create?
Dr. Green: I think he would have said, “Told you so.
Told you so.” He had it right. I mean, Darwin had it right. You know, he did -- genomes;
that word had never been invented -- didn’t know about DNA. He knew something was going
on. He just didn’t know where all that information was being coded. And he knew it was somewhere
and he would look at the Gs, As, Ts and Cs and would see the changes. He would be able
to follow it and he’d say, “Wow. I knew it was somewhere. I just couldn’t figure
out where.”
Dr. Felsenfeld. And I think that he would be telling us what
to sequence next.