Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting October 17th. I am Steve Mirsky. This week on the podcast: From people to chickens to yeast. We'll talk with Scientific American news editor, Phil Yam, about people and animals and public health and evolutionary biologist, Sean Carroll discusses some fascinating research, he just published that looks at how a single gene with two functions wound up as two genes with specialized functions. Plus, we'll test your knowledge about some recent science in the news. First up, though Phil Yam. We spoke in the library at Scientific American.
Steve: Hey Phil. How are you?
Phil: Good Steve.
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Steve: So you just got back from Europe. Where were you?
Phil: I was in Salzburg attending the Salzburg Global Seminar on Animal and Public Health.
Steve: Animal and Public Health?
Phil: Yes. Basically 75 percent of all the emerging diseases come from animals, and the seminar which brought together a group of diverse researchers, tried to look at what we can do to better contain or spot potential outbreaks.
Steve: Now this is a particular interest of yours, because you wrote a book about mad cow disease.
Phil: Right, I wrote a book a few years ago about mad cow disease (unclear 1:12) although this meeting in particular focused the thing more on influenza and viruses, the kinds of things that can happen when you bring together people, pigs, chickens and other animals; human encroachment into the environment, global food production, all these factors come together and create new risks that nobody had really thought about before.
Steve: So, what are some of those risks that nobody thought about?
Phil: Well, the risk is really that, how can we actually find out, discover some of these outbreaks and stop them before they happen. There is no good surveillance at this point that applies to the entire world. I mean, a lot of our food, as you know, comes from China, lot of the food industry has gone global. It's hard to control food production and food quality in other parts of the world. So, the question then becomes, well, how do you actually install [a] surveillance system that applies to everyone equally and create some enforcement of laws in the United States, for instance, in your country, but when once you are gone global, it's a little tougher.
Steve: So far though, it really sounds like you are outlining the problem in more detail rather than really offering solutions, rather than
take[taking] that into account.
Phil: Right. I mean, it's hard to come up with a solution. This meeting really was trying to start a movement, and especially among the organizers who really decided that they are really setting something up for their next generation. They want to push this into a direction, and the common theme of the meeting was convergence; convergence of governments, veterinary science, public health officials and the food producers to really come together and to figure out what is the best way to tackle this. So, their vision statement ultimately boiled down to optimal global health in bracing the interdependence of human, animal, and the environment. So, the question is how do you get there? The group identified several strategies including raising social awareness, better education for human physicians in particular, who in most cases don't have any veterinary science training at all.
Steve: It raises an interesting point about something that most people probably won't think about, but [that is that] veterinarians have a really important role in human health.
Phil: That's right. That's absolutely right, and one of the big problems cited at this meeting was that there is a lack of recognition among public health officials of how crucial veterinary science can be. Several of the participants said that, you know, basically veterinarians get, you know, play second fiddle. They are not
asviewed as high on the social totem pole as human physicians and when it comes to public health, they don't get that kind of funding they need to do epidemiology. In Hong Kong, where there was the avian flu outbreak in 1997, now, its back to status quo, no one has changed, even though, back then it was really feared that avian flu could jump to humans, so things haven't changed, even though people kind of recognize that veterinary science really should play a much bigger role.
Steve: I know that when West Nile first broke out here, it was the veterinary community specifically, Tracy McNamara over at the Bronx Zoo, the pathologist then at the Bronx Zoo, who really figured out what the disease entity was,
andbecause they were seeing it in birds, while the medical community was seeing it in people.
Phil: Right. So, part of the goal
sof this seminar was to find ways to get the groups to communicate better, to find ways that one group should be aware of what another group is doing.
Steve: What else did you come across at the meeting that struck
toyou?
Phil: What was interesting was that to me there is an assumption that a pandemic is going to occur, and
inthroughout history, we've seen cycles of pandemics; I mean, the most famous one is 1918 global pandemic, but there are other smaller ones throughout the '50s and '60s.
Steve: That was a flu pandemic?
Phil: Yes. We are talking about influenza.
Steve: And you thought that maybe the conditions in World War I, worldwide were unique, in that, you know, they obviously were part of why that pandemic got so big? But any thinking that you know the trench warfare, the crowding, the amazing number of wounded, were those conditions that just combined for a unique overall condition that really made that unusual, maybe we shouldn't worry so much about a gigantic pandemic again, without replication of that.
Phil: Maybe so, but in the 21st century, I think, [the] fear is that it will be worse because we have global travel, airplanes, people are going back and forth all the time, we ship animals across nations, so things move around very, very, fast now, and once they get out, if you don't spot it in time, they get out and they can really take off. So I think the fear is now that we have laid the groundwork for a much, much faster-acting pandemic than we had in 1918.
Steve: Yeah, the fear
ofstarting about 20 years ago was somebody with Ebola in Africa gets on a plane to get off a plane in Chicago; that actually happened once, I think.
Phil: Right.
Steve: But, it didn't spread anyway, and the fear was, you know, an Ebola epidemic throughout the Midwest in a matter of days; but so far so good.
Phil: So, I mean, I think that is one of the problems touched on at the summit was that we have a lot of warnings about potential pandemics—swine flu back in the '70s in this country, avian flu—and there is the real threat of people becoming lackadaisical and not taking any of this seriously after a while. For something like this in terms of you know, the nexus of animal and public health, in a lot of ways, I think the food industry should take the lead on this. They are the ones with the money; they have a lot at stake. There was a representative of Cargill at the meeting and they seemed to get it, but the other big food producers, it's not clear to me that they really understand that this is something that they need to worry about; I mean, they produce so much food overseas that if [they're] not taking it seriously and hoping that things remain the same, then I think they are setting themselves up for a real potential disaster.
Steve: If they think it's expensive to try to prevent it, wait till they pay for dealing with it when it happens.
Phil: Right. I actually have some numbers here. For instance, SARS resulted in a thousand
sdeaths and led to 500 billion U.S. dollars in economic loss. An avian flu outbreak, if it jumps to humans, is estimated to cost a trillion dollars in economic loss. So, we are talking some real numbers here, that when things, if things actually hit the fan, we're going be paying through the nose.
Steve: Sure and I mean, even if the disease never jumps to humans, if you have a global pandemic just affecting poultry, that's hundreds of billions of dollars in economic losses.
Phil: Absolutely. I mean, chickens are [a] huge food source throughout the world. And [to] have those animals, you know, devastated and people then probably are being afraid to even eat them, it would just cause economic chaos.
Steve: Well thanks a lot, Phil.
Phil: Well thanks Steve, thanks for having me.
Steve: For more on the Salzburg Global Seminar on Animal and Public Health, go to www.tinyurl.com/2rb37v
Now it's time to play TOTALL…….Y BOGUS. Here are four science stories, but only three are true. See if you know which story is TOTALL…….Y BOGUS.
Story number 1: An American shared the Nobel Peace Prize awarded last week.
Story number 2: A new syndrome is people imagining that their cell phones or Blackberries are vibrating in their pockets.
Story number 3: In a related story, a study found that strippers who are ovulating get a lot more tip money than those in other points in their menstrual cycles.
And story number 4: Bears aren't the only large mammals that love honey—elephants have been found raiding bee hives to get at the sticky sweet stuff.
We'll be back with the answer; but first, ever wonder about where all your genes came from, other than mom and dad? In addition, to random mutations of existing genes, every once in a while, entire genes—even entire genomes—get accidentally duplicated and all of a sudden, a new gene or a whole new set of genes is available for evolution to work on.
University of Wisconsin evolutionary biologist Sean Carroll just published a paper that tracks how one gene with two functions became two genes with one function each. To find out more, I called Carroll, Saturday at his home in Madison, Wisconsin.
Steve: Professor Carroll, good to talk to you today.
Carroll: Nice to talk to you, Steve.
Steve: So, you have this paper in the most recent issue of Nature. It's a really fascinating look at sort of the history of the evolution of a particular gene or set of genes and you did the work in yeast. Let's talk about yeast first, for a second. What's so great about working with yeast?
Carroll: Well, natural selections works on very tiny increments of differences in performance between organisms, and to measure those differences requires a whole lot of sampled life. So, if I would try to do this experiment with elephants or even fruit flies, I would need enormous numbers of animals and enormous numbers of animal counter[s], and a tremendous amount of money; but to do this experiment in yeast [is much easier], because we can grow billions and billions of yeast over night. We can measure very small differences in strains of yeast that differ by very small genetic changes. We can measure those differences essentially overnight and that allows us to then understand the process of natural selection in depth, you know, in great powered, but a much more affordable pace and over a time span much more compatible with a professor's career.
Steve: (laughs) Right. I mean obviously, you are not going to do the work in elephants, but even fruit flies, you'd need a lot more area to store your samples in the generation times that are a lot longer even working with something that has generation times on the order of months, right?
Carroll: Yeah! I think I figured that we'll probably need about a football stadium full of fruit flies to do this experiment. So I think that's a little too many to count.
Steve: I mean you could have had that last Sunday after Illinois beat Wisconsin.
Carroll: Thanks very much for that.
Steve: (laughs) Sure. So you're doing the work in yeast and you are looking at this particular gene construct and an ancestral version of it. Why don't you give us the whole background here?
Carroll: Right! So, I'll just say a little more about why yeast; which is, over the decades, yeast molecular biologists have devised so many powerful tools that allow you to make very precise changes in yeast, in their DNA; exquisite control, where you can change a single base that you want in a particular place, you can put a whole gene in, take a whole gene out, swap genes etc. So what we did is we wanted to ask what happened in the history of a pair of gene[s] in, regular role, brewer's and baker's yeast that is used these days. There are a series of genes that help to manage a particular nutrient and one pair of gene[s], well you know from having the genome sequences of a lot of yeast, one pair of gene[s] evolved from a single gene about 100 million years ago in yeast history. And those two genes today that carry out fairly specialized roles in the use of this particular nutrient, but they were together encoded in the same gene—these two functions were encoded together in the same gene in the ancestor; and what we wanted to figure out [is]
whatexactly how these evolutionary changes had happened, how one gene became two.
Steve: Let's talk for just a second. Now these two genes—just for anybody keeping score at home, they are called GAL1 and GAL3…
Carroll: That's right!
Steve: … and they are involved in the use of the sugar, galactose and they are—to this day—they are about three quarters identical with each other.
Carroll: That's right. And one of the proteins, GAL1 is an enzyme and it sort of harvests the galactose in a way that they can modified in a way they can be used for energy. And the other protein, GAL3, is a regulatory protein; it's involved in turning the levels of the enzyme, the production of the enzyme, way up in the presence of galactose. So yeast, [as] I am sure [is true] of most microbes, they don't want to waste energy making proteins they don't need. So it's only in the presence of galactose that this all these machineries are kicked into high gear.
Steve: Okay. So, the GAL3 is a sensor that lets the system know that it should turn up the production of the protein that GAL1 codes for.
Carroll: That's right. And in the ancestor, these two functions were together in one protein; so the protein was bifunctional and it was both a sensor and an enzyme, but that's somewhat of a constraint because it could be that certain mutations that could make it a better sensor or could make it a better enzyme might make it a worse enzyme or a worse sensor, you understand—vice versa. After the gene was duplicated—now I just mention[ed] that duplication takes place all of the time, they are common sort of genetic accidents—but after the genes were duplicated, now there was the opportunity to divide the labor that was once stored by a single gene; now divide that labor into two genes, and what happened is, a series a mutations have taken place that has optimized each role—
thatthe regulatory sensor role of GAL3 and the enzymatic-converting role of GAL1. And what we did is, in order to figure all this out, sort of trace the path of evolution, we did a whole bunch of sort of, swapping experiments, where we swappedGAL1 for GAL3and we swapped the ancestral protein type of protein in for GAL1or for GAL3, and we even swapped the GAL1and GAL3in for the ancestral protein, in another yeast that didn't have the duplication take place; and from this whole series of experiments, we really expected to find out pretty much how the proteins have changed; and the surprise was that most of [the] adaptive change that had taken place wasn't in the protein, it was in how the two genes were regulated.
Steve: So explain that. It wasn't in the actual sequences of the DNA that would code for the finished protein product?
Carroll: Right!
Steve: The changes were in those other sequences that determine how those genes get expressed, when they get turned on and off and in what numbers.
Carroll: That's right. And so we were expecting that, pretty much you explained the difference between these two proteins actually, in the protein sequence, and some changes have taken place there. So for example theGAL3 protein no longer has any enzyme activity, so that [had] fallen away over time, so that's no great surprise. What we were surprised to find out was that the real differences we could detect in terms of when we did the swap experiments to say which yeast could outperform the other—what we learned was that the GAL1 gene, that the part [of] that, the DNA sequence is outside of the GAL1 gene, it acts as a switch to turn up or turn down GAL1 expression, that had evolved considerably from the ancestral situation; and same for the GAL3.And then what had happened was that each function had been optimized, that GAL3 had sort have been tuned to be sort of a loosely regulated kind of available anytime sensor of galactose and GAL1 had evolved to be
anincredibly tightly regulated, in fact, it's the most tightly regulated gene you know of in yeast. That is, it induced a thousand fold in the presence of galactose that would tightly shut off in its absence. And the mutations that maybe two genes regulated differently—we gathered various sorts of hints that those mutations couldn't have happened with just a single gene. When a single gene exists in the ancestral mutation, that would have made for higher levels of enzyme expression, would have messed up with sensory function.
Steve: So they won't be selected for those mutations.
Carroll: That's right. So what this shows is it sort of gives us a window to say, well, one way the gene duplication allows novelty or specialization or adaptation is by having more genetic parts to work with—each part can be optimized and specialized in a way that if you just have one part, you can do.
Steve: So you also compared it to, instead of having one guy trying to do a whole bunch of different jobs, you've created an assembly line with specialization.
Carroll: That's right, that's right.
Steve: So, this gene duplication business is so interesting and it has such profound importance in evolution and researchers realize that, but I don't think that news has really gotten out to the general public in a lot of ways that in the modern evolutionary theory play book, gene duplication has a really big role.
Carroll: Right! I think, you know, biologists have been onto this for several decades and, you know, we've been looking at the signatures, sort of the outcome of these duplications event[s]; you know, when we look at human genes and you know genes of lots of other organisms that are important to us, you know, medically or agriculturally, things like that; but really, teasing apart sort of the step by step process of how one gene becomes two different genes, that's been hard to do experimentally. I mean, we work and also we get a snapshot of what happens long after the duplication event, but not much of sort of the movie of the step-by-step changes that are taking place. But you asked me right, the importance of gene duplication; most—I say, most, [which] is a rough number—but a very large number of the genes that carry out functions in our body are parts of [the] family of the genes, members of [the] family of the genes that have expanded by gene duplication. So the things that carry oxygen in our blood stream or
the[that] fight off invaders by our immune system or allow us to see in full color, all of these are members of gene families, where the expanding number of genes has broadened the total capability of that type of protein.
Steve: It's really interesting, and one of the thing you point out in the Nature paper is that when gene duplication was first noticed and realized to be important, most researchers thought that what it did was give you one copy of the gene that could continue performing its original important function, and another copy that natural selection could then experiment with to find a new function. But in your paper you talk about the fact that it might be the case that both genes wander off to find new functions.
Carroll: That's right and we are just understanding that there is a lot more trajectories open, so yeah, sort of a long-standing model, it was just as you said, that you sort of would keep one gene to do all the old jobs and play with the new gene, but it turns out that we are appreciating a lot more. There are many more outcomes possible than that. In fact, one of the most common outcomes, now appreciated about gene duplication, is a little bit disappointing, which is really just the old job gets done by two genes, so they really just share the old job; its like, now you['ve] got two lazy workers instead of one really efficient one. So, it can go a different direction. This is not an example of that. This is an example where each function you know, became optimized, but there are ways, there are reasons why gene duplication can also create nothing new, whatsoever. There are some new answers to the whole process.
Steve: Of course, we should also probably keep in my mind that those two lazy genes that are both doing the same job are in the particular little piece of time that we are looking at them in.
Carroll: That's right!
Steve: In the future, some environmental change could happen, where you do suddenly start saving mutations to one or the other and they do wind up going off in different directions.
Carroll: That's right, yeah! That's right, excellent point. Its still material that natural selection can work with in the future and yeah, there are ways for genes to acquire new functions long after they've been duplicated.
Steve: That's really, I think,
is[the] most interesting stuff in the world. I hope our listeners ha[ve]dtoo, and I thank you very much for your time.
Carroll: Thank you, Steve.
Steve: Sean Carroll's paper appeared in the October 11th issue of the journal, Nature. His coauthor is Chris Hittinger, and the article is called the "Gene Duplication and the Adaptive Evolution of a Classic Genetic Switch".
Now it's time to see which story was TOTALL…….Y BOGUS. Let's review the four stories.
Story number 1: An American shared the Nobel Peace Prize.
Story number 2: People often only imagine that their electronic device is vibrating.
Story number 3: Ovulating strippers get bigger tips.
And story number 4: Elephants are raiding beehives for honey.
Time is up.
Story number 1 is true. American, Al Gore, did indeed share the Nobel Peace Prize awarded last week. Nevertheless, the reaction by some parties in the U.S. to Gore's Nobel Prize was less than enthusiastic. One would have thought they would be proud that one of their countrymen was given such a prestigious award. For more check out the blog at blog.SciAm.com, and the article in the August issue of Scientific American magazine called, "The Physical Science behind Climate Change".
Story number 2 is true. More people are reporting the sensation that their phone or Blackberry is vibrating, when in fact it isn't. I know this actually happens to me fairly regularly. The sensation has been dubbed "ringziety" or "fauxcellarm"—that's f-a-u-x-c-e-l-l-a-r-m. An associated press article noted that Dilbert's Scott Adams is also regularly victimized. When it happens, he said he thinks, "Ooh! Its an e-mail with good news",but he says, "so far the only good news is that my pocket is vibrating, and that's okay because it gives me hope that the condition might spread to the rest of my pants."
And story number 3 is true. Strippers who are ovulating got bigger tips, according to a study out of the University of New Mexico that was published in the journal Evolution and Human Behavior. For more info, check out featured news bites of the week on our Web site.
All of which means that story number 4, about elephants raiding beehives, is TOTALL…….Y BOGUS. Because in fact one good way to keep your village elephant-free is to keep bees. Elephants are afraid of the little buzzers. For more check out the October 16th episode of the daily SciAm podcast, 60-Second Science.
Well that's it for this edition of the weekly SciAm podcast. Check out numerous features at our Web site, including Weird Science, the photo gallery and the latest science news, all at www.SciAm.com; and you can write to us at podcast@SciAm.com. For Science Talk, the weekly podcast of Scientific American, I am Steve Mirsky. Thanks for clicking on us.
Web sites mentioned on this podcast include: www.tinyurl.com/2rb37v, www.tinyurl.com/2sj6bf; www.seanbcarroll.com
