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Fishing for Genes by Andrew Kerr September 2006 Take one look at his photo on his departmental web page and you'll immediately realize that Dr. Todd Streelman is a very laid-back guy. Perhaps this is because he spends a great deal of his time working with fish, a task he admits is "very therapeutic." As an Assistant Professor at Georgia Tech's School of Biology, Todd is studying a fish known to aquarium enthusiasts everywhere: the humble cichlid. But in a single lake in Africa there may be as many as 1000 different cichlid species (that's a lot when you consider that there are only about 700 species of birds in the entire United States). This makes cichlids ideal subjects for genetic research, as we discuss in the interview below. |
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(To save this video to your computer, right-click on this link and "save target as". You can also watch it on YouTube.) In addition to answering questions about the development of fish, Todd's lab is also unraveling secrets about genes that could actually impact our own lives. The following interview was conducted September 2006. It may get a little technical for the average high school classroom. So I enlisted Nikolai Curtis, Todd's 2006 GIFT fellow and a high school teacher, to share his views on how to apply this research to the classroom. QUESTION: 1000 species of cichlid have emerged in Lake Malawai in the last 500,000 years, some more recently than others. How do you determine when exactly a species emerged? ANSWER: What you need to be able to do is set a clock with a DNA marker. So you take the same gene that you've sequenced from a number of species in the lake and you look at the number of differences there are. For many of these genes we know that they evolve and mutations occur in sort of a clock-like fashion. You can predict on average how many mutations will occur in some amount of time. So all that you then need is some way to set your clock. The geological record will tell us when the lake was dry. So if you assume that everything that's now living in Lake Malawi and doesn't live anywhere else evolved in the lake once it filled up with water, and if the lake was dry one million years ago, then we can say that some number of mutations occurred in so many millions of years. So you set the clock and then you compare that to the number of mutations that actually separate species that you're interested in. So you say OK, the clock says ten mutations equal 500,000 years, and there are 10 mutations that separate all Lake Malawi species, and so you say OK, then they must have shared a common ancestor 500,000 years ago. Q: It's almost like a radioactive half life for genetics. A: That decay process is sort of the way mutations are modeled in this case, so mutation follows this Poisson Distribution similar to radioactive decay--that's right. Q: According to your web site, you may be witnessing the emergence of a new cichlid species. A: Cichlids have this very interesting breeding biology where every species in Lake Malawi is a maternal mouth brooder. What that means is that the females lay eggs and then immediately pick them up in their mouths. She'll drop them usually on the rock reef where she lives. So there's very limited dispersal. Fish do not swim a long way. And so on each side of a 1 km island we found genetic differentiation between this introduced cichlid. So it came to the island maybe 40 years ago, it took about 20 years to circumnavigate the island, and then either because the environment differs on each side of the island, or because they hybridize on one side and not the other, they're now genetically differentiated on each side such that if you look at gene frequencies here they're different than gene frequencies on this side, and they actually exhibit different color patterns. These color patterns are also very important in mating; females recognize males for breeding based on color patterns. So we think that we're catching speciation happening. Q: People who are doubtful about the emergence of new species might say, "Great. But even if they're isolated and don't choose to breed with one another, they're still the same species. Nothing new has really happened." So, keeping that in mind, what is the definition of a species? I recall something about if two animals breed and create fertile offspring, they're considered members of the same species... A: So this is a huge debate even among evolutionary biologists. Some people say if you sequence a gene and there's this percentage sequence divergence then they're two species. Because sometimes genes evolve at different rates that doesn't always work well. What you're talking about is the biological species concept, and that is this idea where if you take two things and you try to breed them and they actually make viable and fertile offsping then you would say that they're the same species. Now the problem with that is that for one it doesn't work for asexual organisms. Secondly, it doesn't work incredibly well for things that live in disjunct distributions, because in fact they're isolated physically, probably separate species, and you have to take them out of their natural habitat to perform this test. When you take things out of their natural habitat to perform the test, what you get away from are all the interesting mechanisms of speciation that you see if you're in the natural habitat. Because the Lake Malawi cichlids have evolved so recently, they have not built up many of the genetic incompatabilities that cause hybrids to be infertile or inviable. So I can bring them into my laboratory, in fact this is one of the things we do, we take things that are good species in the wild, and we can give them no choice about their mates, and they will interbreed. However if you were to put them in the field or even in a tank in my laboratory and you give them a choice, you take a female species A, and a male species A or species B, and they have slightly different color patterns, this female species A will choose the male and breed with the male species 100% of the time. She will not make a mistake. Now if she's using, say, a blue color as this cue, and you take away the wavelengths of light that allow her to see blue in the laboratory, she will make mistakes, and then those hybrids will be viable. But if you give her the opportunity to visually assess these males, she will almost always choose correctly. A classic example of how that has sort of gone awry in cichlids is a study published in Science in the 1990s where in Lake Victoria, because of wars around Lake Victoria and human perturbation of the system, the lake got very cloudy, and the Lake Victoria cichlids could no longer use color as cues for mating. So there was massive hybridization and the cichlid flock of that lake is very different now because many species interbred at that point. Now the lake has gotten more clear, and species are beginning to mate assortatively again. Darwin's finches do this a lot also. If there are El Nino events that affect the Galapagos, they either bring heavy rains, which cause different sorts of plants to grow which have different kinds of seeds or they cause dramatic droughts, which cause different kinds of plants to die and change the distribution of seed. You'll often have different species of Darwin's finches hybridize. And then after these disturbances go away species start to mate assortatively again. So evolutionary biologists are clearly rethinking their ideas of what species are. We now have a pretty good appreciation that for evolutionarily recent species species barriers are often pretty leaky. Q: It sounds as if some of your research is connected to gene therapy. A: We used some techniques to genetically map the region of the genome in cichlids that controlled biting strength. And it's this engineer's term, we call this mechanical advantage. So any lever that an engineer designs or that is part of a bicycle or a see-saw, a see-saw is a classic example of something that has mechanical advantage, so most see-saws have the fulcrum right in the middle, and I'm sure you played these games when you were little where you have a really big person on one end of the see-saw, and so the only way to get that big person in the air of course is to put more people on this end or to move the fulcrum closer to that big person so that you have more torque and greater mechanical advantage. Cichlid jaws are set up this way, except the jaws themselves are not planar with a fulcrum. They are actually at a right angle to one another. By manipulating this length versus [that] length you basically do what I just described with the see-saw. So when this length gets long, muscles pull here and pull this jaw shut in this direction. But when this is short and this is long, you pull here, you get a lot of speed on this angle. And so what we did was we were basically able to determine the region of the genome that controls that ratio of those two lengths. And we found that in that region of the genome was a gene called bone morphogenetic protein 4, or bmp4. So if we inject more bmp4 into an embryo we should get a greater amount of change than we see before injection. These techniques are quite difficult and they're not developed yet for cichlids, so what we did was we moved to another experimental organism, the zebra fish, and that's where we did this work that you're talking about. So we overexpressed bmp4, we injected bmp4 protein into a zebra fish embryo. Now the neat thing about zebra fish, I was telling you before about this angle here and we'll just call this part here the end-lever, and I say that because the muscle pulls here and closes the jaw shut so this is out-lever and this is end-lever. All cichlid embryos have some end-lever, it's not always super long, but they have something there. Zebra fish embryos don't actually have much of an end-lever at all. They just have this little nubbin. They're modified for speed. So they have a long out-lever. When we injected bmp4 into zebra fish embryos, the embryos grew an end-lever, and that was exactly the phenotype that we had genetically mapped in the cichlids. And in fact studies that other people have done on things like birds and of mice would also indicate that bmp4 has this role in jaw cartilage outgrowth. So you would think only things that have cartilage or bone probably have this gene. But you'd be wrong. Invertebrates have homologs or orthologs, or things that are homologous to bmp4, and it just has a different function in an invertebrate, as invertebrates and vertebrates diverge from one another their common ancestor clearly had this orthologous gene, and it has developed different functions in different lineages. And this happens over and over and over again, this is not unusual, there are gene families that you can trace all the way to things like jellyfish. Why do jellyfish have these genes that in humans code to make a brain? Jellyfish don't have a brain, they have neural nets, and that's sort of what the genes do in some of these invertebrate ancestors. They're always doing something relatively similar but they've been employed in slightly different ways in other organisms. Q: What's it like working at Tech? A: In the two years that I've been here, I've been fortunate, I have a really good lab group now, and one of things that I've been trying to do is to build a group of people with expertise in different areas. So I have a postdoc with expertise in ecological biomechanics. I have a postdoc who came from a mouse neurobiology lab in London whose expertise is the developmental biology of dentitions. And I have students who are strongly in ecology or strongly interested in genetics and then I have some great colleagues here who are interested in engineering approaches to things. So it's actually been, we have a very good group where each person knows a lot about his or her expertise and then we sort of teach each other lots of things when we try to figure out what's going on sort of in the cychlid world. That's been a great part about being here at Georgia Tech. Q: Any advice you'd give to high school students out there? A: I think what I find when I talk with college students at Tech is that many of them I think are already, already have decided at least they think what they want to do before they can figure out what interests them the most. And a lot of this happens because we ask students to get a major early and if you want to go med school you have to do certain things early. And it also happens because when people tell their own personal histories those histories are sort of revisionist histories and you don't always hear how people got into what they do or how many twists and turns it took to get them where they are. I mean clearly my own history was not a straight line to evolutionary development genetics. And almost no one's history is this straight line to something, and if it is it sometimes is a straight line to something they don't like. So usually my advice is often to just relax because students at Georgia Tech are very competitive and they're also incredibly goal-oriented, and sometimes that's good, like that's good in a class where the goal is to get a good grade and they know what to do to get a good grade. But sometimes that carries over into "Well, I have to take these classes and I have to take the MCATTs at this time." So I mean my best advice would just be to take classes that you think will interest you. Of course make sure that you follow degree requirements there are mechanism to get students into laboratories to do research here as undergraduates. When you're a high school student or a college student almost nothing is the end of the world. I know many things feel like it's the end of the world but almost nothing is the end of the world at that point. I've talked to my undergraduates who had birthdays and they're like 22. They have their whole life ahead of them! And they are many times more organized and way more together than I was at their age, and it amazes me. And so sometimes my advice is just sort of relax and enjoy yourself, figure out what you like. We try to regiment things, and sometimes students get caught up in that. It's probably better just to follow things you like. Q: Did you ever experience that end of the world feeling? A: When I was in graduate school like I mentioned earlier I went to graduate school I chose the place where I went to graduate school because I was working with a person who studied the functional aspects of shape and I had worked in this person's lab for two years, and the product I was working on wasn't working out and I thought I would be able to X and I couldn't do it, and I was discouraged, and I felt I was two years into my PhD program and I felt like I wasn't maybe as interested as I should have been and things weren't going well and I was doing all this reading about genetics and all this kind of stuff, and so for a short period of time I thought yeah this is horrible, I'm doing this and I don't want to be doing this anymore. And when I finally had the courage to bring that up with my advisor he's like, Todd, this like happens all the time! Go talk to the geneticist down the hall! I did and I got into his lab and I started doing that. It's no big deal. Q: Were you always interested in fish, or did fish just sort of happen in your research? A: I grew up on a river which is a tributary of the Chesapeake Bay so I used to catch fish all the time. So it probably started there. But then it was really solidified when I took an evolution class as an undergraduate and I loved it and then I went to the marine biological laboratory in Woods Hole, Massachusetts, and it was there that I actually first got my hands on cichlids because again this is all serendipitous but I had a teacher who was working on cichlids and had this big loan of preserved specimens from one of the museums at Harvard. I got to do a little project for him, and that's where I also sort of got to play around with the jaws to see how they worked and stuff like that and that's the first time I decided what I wanted to do. But subsequent to that I'd done projects on nemotode worms, I'd done projects on DNA of other organisms and so to me it's the question that drives the research. And if cichlids are not where the question takes us we'll start to work on something else. So I still think if you had to ask what the general theme of the lab is now the theme is trying to understand how development works. If you came back and talked to me in 10 years I'd probably be doing different things. We're already trying to figure out, the lab has a two year plan, the lab has a five year plan, the lab has a ten year plan, so if you come back in 10 years we'll be studying cichlid brains, I can almost guarantee it, that's the ten year plan, I don't think we'll be doing jaws nearly so much. And it's great because I will get to learn about a whole new set of things so that's why we do what we do because we are constantly learning about stuff and what means is that you're constantly changing focus, and I think that's sort of natural for humans sometimes, and it happens throughout your life. So when people get regimented into these things I think sometimes that is counter-productive. Q: Where around the Chespeake did you grow up? A: I grew up in a town called Chestertown which is on the Chester River. So it's the eastern shore of Maryland. So across the Bay Bridge from the big cities of Washington and Baltimore. Q: I grew up in Northern Virginia. I used to take birdwatching trips out there. It's a real haven for wildlife. A: It used to be. [Laughs] Q: It used to be? A: Well I think the bay is, the Chesapeake Bay is the largest estuary in the United States, maybe in the world, and it's sort of making a comeback but I think it's also one of those that is one of the most polluted. So yeah. Q: Too bad! A: [Laughs.] Q: Have you been able to travel to Africa? A: Yeah. I've been to Malawi twice, and I took the lab two summers ago, two summers ago we went, and there's a great field station right on the lake that's run by the university of Malawi and so we rent the field station, and the field station has boats and scuba gear and scuba tanks and they have two boatmen, they have cooks they have watchmen. So it's some of the easiest fieldwork I've ever done. And Malawi is a former British colony, so everyone in the country speaks Queen's English, so they actually speak better English than I do. We go there to study the evolution in action questions that we talked about early on in the interview, that we actually have to be on site to make collections in specific places. Other than that there is reason to actually go less frequently because when we go we collect a lot of fish and sometimes that's unnecessary, some of these species are fairly fragile, and-- Q: And you're changing the order of things over there. A: Potentially, we're potentially changing the order of things by removing things from the lake, so the less we can do that the better. And so for many of the models that we use to study development or some of the genetic work that we do we just get fish exported directly to us. Q: Seems like all this is also a lot of fun! A: It is fun. People often write about going to places like Africa and having this reawakening and stuff like that because you sort of see life in just a rawer form. Everything there is, it just seems much newer and much younger even though it's a real old continent, it just seems new and different and so it's fun, it makes you think about things in slightly different ways. It's fairly easy to live there and you make a lot of friends from the little town where we stay. Which is always nice, too. Meet Todd's 2006 GIFT Fellow, High School Biology teacher Nikolai Curtis. Georgia Performance Standards (-- Show --) |
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