Stop bugging me! The genetics of bedbugs and other insects
They suck your blood, hitch-hike on your luggage, and are a growing threat to the hotel industry. Bedbugs are a growing problem in the modern jet-set world, and scientists are using genetic techniques to try and understand why. Feeling itchy yet? Plus, we look at the genetics of some other annoying insects, get to the bottom of the recent controversy about junk DNA, and our gene of the month is none other than Superman and his weedier alter-ego Clark Kent.
In this episode
01:10 - Bedbug genetics
with Toby Fountain, University of Sheffield
Kat:: Our first guest, Toby Fountain is responsible for one of the least pleasant experiences I've had for a long time when he took me into the bedbug breeding room in his lab at the University of Sheffield. I asked him to explain the growing bedbug threat, how genetics can help us to understand infestations, and what we can do to prevent picking up these unwanted invaders.
Toby:: Bedbugs were pretty much everywhere until about 1940 and then with the introduction of better public health legislation and powerful insecticides, they were pretty much wiped out across the western world. Then we found that just after 2000, reports started resurfacing again, and it looks like the bedbugs are now making a bit of a comeback. But it's become a bit of a mystery. No one really knows why. Why now? Why have they been in obscurity and then suddenly come out? So, what my research is basically looking at is the potential mechanisms for their resurgence.
Kat:: So, how do bedbugs spread around the place?
Toby:: So, the interesting thing about bedbugs is that they're flightless. So, they can't move very far under their own steam. So, what bedbugs actually have the sort of nasty habit of doing is hitchhiking in our belongings. So, you might go to an infested hotel for example and the bedbug may crawl into your bag or into your clothes. It's then very easy for you to jump on a plane or jump on a train, and that bug can be dispersed a huge distance, and that's how it looks like they're probably spreading.
Kat:: They feed on us, they suck our blood at night when we're asleep. Is this a particular health risk?
Toby:: It's probably more of a mental health problem than a physical [one]. They don't take a huge amounts of blood, but it can give you quite severe reactions. So, reactions vary from person to person, but you can be bitten multiple times by one bug and might have hundreds of bugs at your property. I think the real problem is, it's striking you at your home is the thing and there's no real escape from there. So I think the psychological distress is more of the problem. And it's also the economic problem for both people trying to get rid of them, but also, it's had a massive cost for the tourist industry. Obviously, if a hotel is found to have bedbugs, people aren't going to want to go there.
Kat:: And I'm slightly freaking out just sitting here, talking to you. It's not very pleasant. How are you trying to study how these populations have spread around the world recently?
Toby:: So the cool thing that we can do is actually use genetics in order to track their dispersal. So what we do is basically DNA finger-printing. So, it's quite hard to finger-print a bedbug, so what we do is we take samples of its DNA and we look at variable regions across its genome. We can then compare different individuals at these variable regions and we can come up with an idea of how related the individuals are. So for example, if we find you've had bedbug infestation at say, a hotel, we can genotype the bugs from there, and then also, genotype a bug that you may have thought you've brought home. Then we can match them and see how likely it is that they came from the same place. So this has a lot of practical applications because it means that in lawsuits and other things like that, we can prove that bugs have likely come from a hotel. So, it means that people aren't getting wrongfully sued for it.
Kat:: So obviously, a bedbug is very small and humans are very big, and they don't drink a lot of blood. Why do they need to disperse of they found a nice place where they can live, where there's lots of humans? Why do they feel this need to travel the world?
Toby:: So, we've been looking at a few possible answer to that. So, one thing we looked at, whether inbreeding was playing a role. So, a lot of animals will actually disperse to move away from their brothers and sisters in order to avoid mating with them. The other possibility is that it's actually a lack of space. So, what looks to be the driving factor is actually that bedbugs don't actually live in the bed a lot of the time. What they'll do is they'll live in small cracks and crevices surrounding the outside of the bed. It looks like that these cracks and crevices actually have a certain capacity and once they've reached this capacity, a bug has to move a bit further away. And it looks like as infestations become occupied, that becomes the driving factor, the search for space to hide away. It's also why it looks like if you go to hotel and you leave your bag near the bed for example, that's the ideal place for a load of new harbourage space for the bedbugs to crawl into.
Kat:: And tell me a bit about what your research has shown so far, so looking at populations of bedbugs and how they've changed around the world?
Toby:: So genetic diversity is a very important thing to look at because it's how species evolve. Having diversity is how you can adapt to new situations and conditions. What we're finding is actually, infestations have very, very low diversity. It looks like bedbugs are very inbred and while for most species that would be a big problem, it seems to not affect the bugs at all. They can still rapidly grow. And it looks like only a few individuals, a very small number of individuals start infestations. So, what we're seeing is that even one female that's been mated multiple times can come to your house or lay a lot of eggs very quickly, and within a few weeks, you could have a big infestation on your hands.
Kat:: Obviously, when you look at species like humans, inbreeding is really bad and we see inbred human populations, and other animal populations having genetic problems when inbreeding. So, this doesn't seem to be happening with bedbugs?
Toby:: So, a few mechanisms that this could be. It could be that, what we see is something called purging. So what happens is that, you have a load of recessive genes - genes don't occur very often - and that these are lost very quickly. So every individual that has this gene die. And so, the genes can't be passed on and are lost from the population. So once you get this purge, the bugs are actually quite successful because they don't have these deleterious alleles in the population. So that's one thing we're looking at as well.
Kat:: What should people do if they're concerned about picking up a bedbug infestation? What should they look out for?
Toby:: So the thing that we really want to emphasise is the importance of being vigilant and just looking out, reducing your chances of picking them when you go to a hotel, and also, looking out for the signs. So if you think you're being bitten, you want to be looking out for sort of brown spots around your bed. When they grow, they shed their skin, so you can also see shed skins around. You want to look around the cracks, around the mattress, around the obvious places that look like bugs may be hiding. And if you can catch them early then they're not as hard to get rid of. And if you're aware, your chances of having a full blown infestation are actually fairly small.
Kat:: That was Toby Fountain from the University of Sheffield.
08:12 - ENCODE, hype and junk DNA
ENCODE, hype and junk DNA
with Nell Barrie, Science Writer
Now it's time to take a look at one of the biggest genetic stories this month with science writer, Nell Barrie. In last month's podcast, I covered a news story about ENCODE, the Encyclopaedia of DNA Elements, which has just been published. Over the past few weeks, a debate has raged over the findings from the project and perhaps even more so, the way they've been reported. So Nell, what's going on here? What is ENCODE?
Nell:: As I understand it, this is a big step on from the human genome project. That was all about cataloguing all of the DNA code in the human genome and this is about what all of those different bits of DNA actually do. Are they turning on genes? Are they parts of genes? Are they regulating genes? All of those kinds of questions. So this is all about finding out what this massive toolkit that we have inside our cells is doing and how it's doing different things inside different types of cells as well.
Kat:: In all the DNA we have in our cells, we have this concept of - I guess it used to be called 'junk DNA' - that there was an awful lot of the genome that wasn't really useful and only a very small percentage is genes. What do these new studies tell us?
Nell:: Well, the big headline that was coming out over lots of the press reporting was that 80 per cent of the genome is doing something. And the question became, "Well, what does that actually mean? What is it actually doing?" Because it sounded like we were saying, "Most of the genome isn't junk after all" which was exciting in one way, but also, a lot of biologists felt like we already knew that. "Junk DNA" is one of those nice little phrases that doesn't really ring true for a lot of scientists. It is really interesting because they're trying to find out exactly what all the DNA is doing, but we don't really have enough information yet to know how it all fits together. So it's almost like, this massive bonanza of information that scientists need to get their hands on and really get to grips with.
Kat:: Because it did seem really exciting. Well, we've got the genes, but then there's all these bits that switch genes on and switch off, bend around, fold up, do structural things, so that was quite exciting. It's also really interesting just to see how they've looked into our genomes because I think we think as humans, we must have incredibly special and wonderful genomes. But just looking at the way they've downgraded how many genes they think we have - do you remember back at the beginning of the human genome project? Was it 100,000 genes?
Nell: Yeah, that was they estimated. They thought that it would turn out humans had about 100,000 genes, and it turned out to be closer to 30,000 which was a bit of a kind of, "Oh, we're not quite as important as we thought we were." Especially when you compare it to other types of animals which you might think of as simpler, but actually, they have many more genes than we do. So for example, I was reading today that salamanders have 10 times as much DNA as a human which seems crazy because they're just these cute little amphibians, but that just goes to show how little we know about what are this DNA is actually there for and what it's doing.
Kat:: So, I think they've taken it down to something like 25,000 genes make a human which it doesn't seem like enough when you compare it to how you make other animals or even other kind of plants and other organisms. But one of the other interesting things about this whole story was the way it was reported because this was a real bonanza for science reporting. They've published 30 or something papers simultaneously with a website and everything. Is this a new step forward for publishing science?
Nell:: It certainly seem like that to me and I thought on one level it was great because I looked at this and thought, it's that really exciting, exploratory blue skies type of science where you don't know what you're going to get out of doing this work, but you know it's going to be really interesting and there's probably stuff in there that we don't even realise is going to be important in the future. So, it's great to show people that side of science and get people excited about it. But on the other hand, there was this need to come up with these really pithy statements about what ENCODE will do for us, like it will solve all disease, it will tell us exactly what the DNA genome is doing, and obviously, it's not quite there yet. So I think some of that got a little bit blown out of proportion.
Kat:: Where do you think we go from now with this kind of research and even with this project?
Nell:: Well, I think it's just a case of, all these data is out there now and it's been produced by this consortium which is great because it means that people can have access to it. Researchers can use the data and they can do whatever they want with. It's kind of the sky is the limit which just your imagination can determine what you can do with this. So, it will be really, really exciting to see what comes out of it in the future, but I think that's probably the way we should look at it is it's a tool for future research rather than, this is an amazing research finding right now.
Kat:: And also I think finally, we have to consign the phrase, 'Junk DNA' to the dustbin of linguistics, do you reckon?
Nell:: Yeah, definitely. There was a lot of commentary on this and I just kind of totally agreed with them and they said, "C'mon, this junk DNA thing really? We've got rid of our idea already." It must be there for something or perhaps it was once there for something that it's no longer doing. But it's just about understanding how everything has evolved over time, how it's still changing. It's not about saying, "This bit doesn't do anything, we shouldn't be interested."
Kat:: Because it's incredible. We have over 2 meters of what's basically biological string in every cell of our body, and it's coiled up in such a complicated way. I mean, I can't believe that much of it would stay in there if it wasn't needed.
Nell:: Yeah, exactly and I think the other thing that I really liked with some of the blog posts I was reading about was this idea that even if you have got DNA that currently isn't doing anything useful, that's almost like the fuel for future mutations. So, it could mutate and change and suddenly do something quite interesting, and maybe that is the way that's fuelling evolution. That could be something that's actually quite beneficial in the future. So, there's a kind of other side to it as well I think.
Kat:: So, thanks very much, Nell. That's Nell Barrie, Science Writer.
13:47 - Stem cells for hearing loss
Stem cells for hearing loss
Researchers at the University of Sheffield, together with colleagues in Thailand, have made a big step forward in developing stem cell therapy for hearing loss, publishing their work in Nature. The team converted human embryonic stem cells grown in the lab into cells known as "otic progenitors" - the precursors of nerve cells known as spiral ganglion neurons in the inner ear, which send sound signals to the brain.
When they transplanted these progenitors into deaf gerbils whose spiral ganglion neurons had been damaged, the animals had a roughly 46% improvement in hearing over 10 weeks, compared with deaf gerbils who didn't get the stem cells transplant. If scaled up to humans, the researchers suggest this might be the difference between only being able to hear loud noises like passing trucks, or being able to hold a conversation. In case you're wondering how you measure how deaf a gerbil is, the scientists measured the animals' brainwaves in response to noise rather than trying to put a tiny pair of headphones on them.
Although this story was widely reported as a "stem cell deafness cure", this research is just a proof of concept for restoring hearing after one specific type of damage, and it's still very early days.
14:59 - Oyster genome sequenced
Oyster genome sequenced
Beloved of upper-class diners everywhere, and a multi-million pound industry in the far East and US, oysters are more than just a pretty shell. Now an international team of researchers from China, the US and Europe have mapped and sequenced the Pacific oyster genome, publishing their report in the journal Nature. The new data reveals how oysters have adapted to life in the sea, and how it creates its complex shell. Life for Pacific oysters is tough, as they live between the high and low tide levels, exposed to the hot sun when they're not submerged in salty water. And there's also the risk of attack from birds and other animals. The genome map reveals more than 80 genes that have evolved over time to help to protect the oyster from stress in this inhospitable environment.
The researchers hope that their work will help scientists breed faster-growing oysters that have a better chance of surviving.
15:52 - How the king cheetah got its spots
How the king cheetah got its spots
Researchers from the US, Brazil, South Africa, China and Namibia have worked together to solve a feline mystery that sounds like one of Kipling's Just So stories - how the king cheetah got his spots, or rather, stripes. Regular cheetahs are covered with small dark spots, while king cheetahs have thick stripes and blotches over their coats, even though they are actually the same species. Writing in the journal Science, the team have tracked down the single gene that turns a spotty cheetah into a stripy one, and it turns out to be the same one responsible for the difference between stripy mackerel domestic tabby cats and spotty ones.
Called Taqpep, a full version of the gene gives tabby cats a stripy mackerel coat, while a mutated version gives them spots. In the case of cheetahs, a different mutation is responsible for the king cheetah's coat pattern. Further research revealed that Taqpep probably controls zones within the animal's skin in which cells called melanocytes produce melanin - the dark pigment responsible for their spots or stripes. Faults in the gene lead to different shaped zones, resulting in different coat patterns - no Just So story required.
17:01 - Allergy-free houseplants
And finally, good news for people who suffer from allergies to Pelargoniums, the popular houseplants. Scientists in Spain, led by the aptly-named Begona Garcia-Sogo have shown that adding two genes into the plants can prevent them from producing allergy-triggering pollen, and make them live longer. Writing in the journal BMC Plant Biology, the researchers used a modified plant bacterium Agrobacterium tumefaciens to transfer the genes into plant cells.
One gene encodes an enzyme that increases the levels of a plant hormone that prevent ageing. The other gene, originally from a pea plants, destroys the plant's anthers - the plant's male pollen-producing organs. Plants carrying the new genes were more compact, with smaller leaves and flowers but more vibrant colours, and lived longer than usual. The modified plants could be interesting to gardeners who want longer-lived displays, as well as sneezy indoor gardeners. The lack of pollen production also cuts the chances of the modified genes being released into the environment. But the additional genes still can't protect the plants against careless owners who forget to water them.
18:26 - Mosquitoes, fruit flies and infections
Mosquitoes, fruit flies and infections
with Dr Frank Jiggins, University of Cambridge
Now it's time to take a look at some other insects. Not only do mosquitoes keep you awake with their annoying hum and painful bites, they're also a major channel for the spread of diseases in many parts of the world including malaria and dengue fever.
At the University of Cambridge, Dr. Frank Jiggins is investigating why some insects are susceptible to infection with disease-causing parasites and why others aren't. As well as studying mossies directly, he's also looking at some rather less annoying and dangerous insects as a model - fruit flies. I started by asking him what sort of diseases fruit flies could pick up?
Frank:: Fruit flies have lots of parasites and pathogens. So, we particularly work on viruses and they also have parasitic wasps which lay their eggs within the fruit fly larvae and then the wasp will develop and devour the fruit fly larva from within. Insects also have a very sophisticate immune system so you sometimes find genetic variation in their immune response. So, some individuals have more effective immune responses. But then also, particularly for viruses, the virus relies on using lots of host molecules and lots of insect molecules in order to complete its own life cycle. So, evolution can change the insect proteins which the virus is using for its own benefit, in a way that makes insects resistant to infection.
Kat:: What sorts of viruses are these that infect fruit flies? I can't imagine a fruit fly with a cold.
Frank:: Well, it turns out that in fact, fruit flies have an enormous diversity of viruses. So, there's only two or three which are well-understood and that we work with in the lab. But in fact, if you look and you sequence viruses from fruit flies, they have a diversity of viruses, many of which are related to things like rabies in vertebrates, and a whole range of other viruses which infect us. So in fact, they have lots of different viruses. Many of which are very similar to viruses which we get.
Kat:: Now, you think that it would be quite a big advantage if an organism, an insect say, was resistant to viruses. Why do we still see such variation in populations? Why haven't the susceptible individuals just been bred out?
Frank:: Yes, so you'd expect due to natural selection that you'd end up with everyone in the population becoming resistant and then you wouldn't be left with any susceptible individuals. So, there's two possible reasons why you'd still get susceptible individuals. So, one possibility is that being resistant is very costly. It might take a lot of resources or you might suffer from autoimmune disease if you have a very active immune system. So it might be that for some individuals, it's better to be susceptible and take the risk of becoming infected to avoid all those costs of being resistant. But one thing which we're finding with viruses, is that the reason why you see so much variation is that the parasite itself keeps changing.
So, as soon as the insect evolves to become resistant, then the parasite or the virus will change and overcome that resistance. So this leads to an evolutionary arms race as the host or the insect needs to keep evolving new ways of becoming resistant. So you get new genes arise or changes to genes in the insect population and these are continually spreading through the population. So, when we turn up and we look at that population, we see lots of variation and that's because the resistance genes are spreading through the population as the susceptible individuals are being killed off by the infection.
Kat:: Tell me a bit about the work you're doing in mosquitoes. How do some mosquitoes become resistant to say, malaria parasites or other parasites?
Frank:: Other people have worked on malaria and they found that there's a variation in some of the immune genes which recognise malaria parasites and that means that some mosquitoes in populations resistant and can transmit malaria and others are susceptible and do transmit malaria. So, we've been working on a mosquito which transmits lymphatic filariasis which is caused by a small nematode worm, and we find we haven't yet found the gene, but we find there's a single gene which controls resistance to this worm. It's got very, very simple genetics. So we're currently trying to identify which gene it is which is preventing some mosquitoes from transmitting the infection.
Kat:: Presumably then, maybe you could breed or select mosquitoes that don't transmit the infection, release them into the wild, and hope that it would reduce the transmission of the disease?
Frank:: So that's really the difficult bit. So finding the genes is the easy bit. So finding out why you get resistance in susceptible things is easy. The difficult thing is then trying to modify the mosquito populations so that they all become resistant. So one possibility people have suggested is you might be able to use some sort of genetic modification which would allow the genes to spread through populations. Another thing which has caused a lot of excitement recently is it's being discovered that bacterial symbionts can also make mosquitoes resistant to particularly RNA viruses which can cause things like dengue fever.
Kat:: What do you mean by bacterial symbiont? What's that?
Frank:: So, these are bacteria which infect insects and they're particularly bacteria in a group called Wolbachia. They're found in about 40 per cent of all insect species and they're transmitted through eggs, so they go from mother to offspring every generation. And the advantage of this bacteria is firstly, they very often protect the insects from the RNA viruses which means if you put these bacteria into mosquitoes, they can't transmit dengue fever. But also, they have tricks by which they can spread through populations.
Kat:: So then maybe if we could spread these bacteria through the population that would also be a really good way of getting resistance.
Frank:: Yes, so what people have done in Australia is they took a Wolbachia which had been first identified in fruit flies and made fruit flies resistant to viruses. They put it in some mosquitoes and there they found firstly, it made the mosquitoes resistant to dengue fever but secondly, they also released these mosquitoes in the populations in Australia and they found that when they'd released enough infected mosquitoes, the bacterium started spreading through the mosquito population. So you can see that hopefully, this might lead to a way in which we could spread the bacteria through natural populations of mosquitoes and potentially interrupt the transmission of diseases like dengue fever.
Kat:: But until that day, we'll just have to keep swatting them?
Frank:: Yes, I think so. I think there's still a way to go before we eradicate dengue fever.
Kat:: That was Dr. Frank Jiggins from the University of Cambridge.
Can gene therapy alter reproductive cells?
Answered by Professor Jo Poulton from Oxford University.
Jo:: It is actually already possible to alter genes in germ line cells and this has already been done in several species including mice, sheep, and cows. That's what would be needed to prevent a mutated version of a gene from being passed on and causing disease. The problem is, we don't know what the long term consequences of germ line gene therapy would be for children born as a result.
It's possible that you might have mistargeted [the gene] and that other genes would be affected in the process when you were correcting an initial mutation. Many people also feel that this sort of therapy would be contravening a child's human rights as they would have no choice whether their genetic material was altered or not and actually also, that they would need to be followed up for long term into adult life to check up on the actual type of correction that's been done. There's also some concern that correcting genetic diseases this way could be the thin end of the wedge leading to designer babies.
But there is a group of diseases, inherited defects, where the defect isn't in the main nuclear genome itself. It's mitochondrial diseases where mitochondrial DNA is affected. So mitochondria, the powerhouses of the cell, they provide energy. They're actually descended from bacteria which paired up with cells about 2 billion years ago and became intracellular power supplies. Importantly, that event means that they have their own genome and many mitochondrial diseases are caused by defects in mitochondrial DNA. Mitochondria are inherited in egg cells, and because of this, the technology now exists to replace the damaged mitochondria that are maternally inherited carrying a disease with an IVF-type technique and this would prevent the baby from inheriting a disease. It would also mean that the child would have genetic material from both parents and from the egg then, so that's a 3-parent family. There's currently public consultation under way in the UK to discuss whether or not this will be ethically sound which I personally think it is. The problem is that because there are other options available which we already know are safe, which we don't know about nuclear transfer, it's likely to be many years before mitochondrial replacement would be offered outside very closely regulated clinical trials.
Kat:: That was Professor Jo Poulton from the University of Oxford. And if you've got any questions about genes, DNA, and genetics that you'd like us to answer, just email them to firstname.lastname@example.org, tweet us @nakedgenetics, or post on our Facebook page, and we'll do our best to answer them.
28:16 - Gene of the month - Superman
Gene of the month - Superman
with Kat Arney
And finally, our gene of the month is Superman! This time, the name comes from the world of plant genetics, as the gene was first discovered in Arabidopsis - a type of cress that's often used as a model plant. Flowers from plants with a faulty version of Superman have extra male parts - the pollen-producing stamens - and fewer carpels, the female seed-producing bits. Superman is switched on very early on in flower development, and it plays an important part in distinguishing these different organs. In 2002 there was an interesting plot twist, when researchers in the US discovered another gene that switched off Superman in plant cells. What else could they name it but Kryptonite? And finally, there's one more related gene - a weaker version of the Superman gene, dubbed - of course - Clark Kent.