eLife Episode 44: Sperm Competitions and Ancient Horses
In this episode, we hear about self-esteem, a new genus of extinct horse, the future of biological engineering, tracking mosquitoes with mobile phones, and how a love rival causes salmon to increase their sperm speed...
In this episode
00:32 - Mobile phones identify mosquitoes
Mobile phones identify mosquitoes
with Manu Prakash, Stanford University
Chris - As the vectors that transmit malaria, dengue, yellow fever, Zika and a host of other infections, mosquitoes are widely regarded as one of the world's most dangerous animals. Yet we know very little about where they are, how they are spreading, and how their distributions influence disease. Now mobile phones may be coming to the rescue. From Stanford University, Manu Prakash...
Manu - You know as many problems, they start with experience and many of us have experience being bitten to bits by mosquitoes. I was in a field trip in Thailand when I met a lot of medical entomologists hunched back on microscopes essentially sorting mosquito species and made a realization that today we actually use the same technology that we were using hundred, 150 years ago to speciate and identify mosquitoes in the field. So the problem has always been is we know mosquitoes are important. I don't have to repeat the number of deaths caused by them with all the diseases and all the implications that we don't actually know for these diseases but we don't know where our enemy is. And that's what we wanted to solve. Could we imagine a new platform that is scalable, very very low cost, and it provides a new window essentially into the life of mosquitoes?
Chris - Why does it matter? Identifying what type of mosquito you're dealing with.
Manu - There are more than thirty-five hundred species of mosquitoes and only a few of them, between 20 to 40 different species are the ones that carry deadly diseases. For many of these diseases, we actually don't even have a cure. So it becomes extremely important to be able to understand where these vectors are. Both for scientists who are trying to understand these diseases but also for municipalities who are trying to reduce the burden of these diseases by reducing mosquito populations
Chris - Because those sorts of authorities have been tracking where the mosquitoes are and in what sorts of numbers by doing things as primitive as just putting out a trap and then counting what they catch haven't they?
Manu - Yeah and you know it's a very effective strategy it's just you need a lot of people to do that. So it doesn't scale to the size of our planet and specially with many of these mosquitoes even spreading their range where they're found. So we need a better solution.
Chris - So what is your solution?
Manu - We've been thinking about this problem for awhile and we stumbled upon a very old known fact which is the fact that mosquitoes fly they generate this buzzing sound and we made a realization that using a regular cell phone you can record these sounds and using machine learning and algorithms we can actually speciate these recordings into specific mosquito species.
Chris - So there is a signature wing beat that goes with a species is there? And you can use that to discriminate them?
Manu - That's correct. And both males and females have different wing beat frequencies and because frequency and sound plays an integral role in how mosquitoes mate they actually play love songs to each other, in fact. It essentially ends up happening that many species have differentiated wing beat sound signatures and with cell phones, what's powerful is you don't just get the acoustic signature, you actually get the location of where that recording was made, the time of the recording. This is all served as metadata and using that metadata we can even improve the accuracy of the classification to be even higher.
Chris - A mobile phone is good enough is it the microphone that's in there is adequate to capture a clean enough signal of the sound in order for you to get the diagnosis of what the mosquito is?
Manu - Yeah and this was a really fun finding. We compared almost five to six different brands of cell phones at different prices and what we demonstrated in the paper is it turns out because cell phones are designed to record and transmit sound, the microphones have been improving over the years to an extent that they are actually fantastic both for capturing the sound and transmitting it and recording the meta data and we demonstrate that they actually compete very well with some very expensive microphones as well to do the job.
Chris - So have you done field trials on this? Have you now got citizen scientists, people out, stakeholders and actually demonstrated that this can accurately tell you what sorts of mosquitoes are buzzing around those individuals at that point in tine?
Manu - Yeah that's always been why we started doing this to begin with is to engage the community and ironically you don't have to be in the bushes to do this because many mosquitoes live in urban environments. When we wrote the paper there is a website that anybody can go to. We've gotten lots and lots of recordings coming from around the world from rural India to Zaqistan to rural parts of United States, all across the world. And one of the big things that we're trying to do is make the tools easier and easier for the community to engage and specially the new sets of tools that we're building on top of this technology is things that provide them immediate feedback, provides them more information about their local surroundings and the types of mosquitoes that they're recording. So this is ongoing piece of work. You can go to our website "abuzz dot stanford dot edu" and you can subscribe and also upload your recordings and very soon we will be releasing an app. Which will allow to integrate this directly in the cell phones that people use.
06:31 - How brains measure self-esteem
How brains measure self-esteem
with Geert-Jan Will, Leiden University
How we feel about ourselves is largely dictated by what we think other people think of us. But just as important as someone else’s opinion is what we expect them to think of us. If we believe that someone should rate us highly and, in fact, they don’t, the dent to our confidence is much greater than a bad rating from someone we expect to mark us down. And Leiden University’s Geert-Jahn Will has identified where in the brain this happens…
Geert-Jahn - We know that our self-esteem is shaped by what other people think of us, but what we didn't know is how the brain keeps track of what other people think of us and then how this is integrated into our evaluation of our own worth. So we set out to study this. We asked healthy young people to perform a social evaluation task while they laid in an MRI scanner. And before they came to the lab they uploaded a personal profile to an online database and we told them that other people were going to look at this profile and that they were going to receive feedback from these people. And while they were in the scanner we showed them the feedback that they had received which actually was a computer algorithm so that we could control the feedback. And people received likes or dislikes in the forms of thumbs up and thumbs down symbols which represented whether the other person was interested to get to know them or whether they thought they were not so interesting. And then after every two or three judgments from these peers, they reported on their current level of self-esteem.
Chris - Now critically did they know about the likely judgment that the person was going to make or was the judgment completely blind to them?
Geert-Jahn - So what we were interested in is not just whether your self-esteem goes up and down. We were critically interested in expectations. So whether you expect to be liked by the other person and how that impacts how you feel about yourself when you received the feedback. The participants in our study interacted with different kinds of people which we subdivided into groups. We used these groups so that participants could learn whether some people were more likely or less likely to give positive feedback. And what we saw in the result is that participants started to expect to be liked by the people in the groups that mostly gave positive feedback and they started to expect to be disliked by those who were more likely to give negative feedback.
Chris - What about though how that impacts on their self-esteem. So if you say to someone you're going to get feedback from this person who usually, 90 percent of the time gives positive feedback but then you say actually they hated you. What does that do to their self-esteem?
Geert-Jahn - Yes, so that is exactly what we were interested in. What we saw is that when participants received a thumbs down by someone who is in general very positive, so when they expected to be like the most, their self-esteem went down the most and the opposite was also true. And we could quantify this sort of level of surprise using a mathematical model. What was sort of central to this mathematical model was prediction errors. They captured the difference between the feedback that you had expected to receive and the feedback you actually received. So we found that self-esteem changes were guided not only by whether other people like you but were especially dependent on whether you expected to be liked.
Chris - It's interesting this because we've all been there haven't we, we know that the professor of biochemistry is very hard to please, but when he or she gives us positive feedback we get a rush of self-esteem feeling very pleased with ourselves because we got feedback from a hard taskmaster.
Geert-Jahn - Exactly. So it seems very intuitive but what is the most innovative part of our study is that we can actually quantify these feelings using mathematical models. And this is important so that we can actually use the model to identify signals in the brain that sort of explain why our self-esteem goes up and down when we learn other people's judgments of us.
Chris - Yes indeed because you had these subjects in brain scanners while you were asking them to rate their esteem in response to this feedback. So what did you see? What was their brain doing in each case and how did that match up with how they were feeling about themselves?
Geert-Jahn - The mathematical model contains the prediction errors that people use to determine their self-esteem. And what we saw is that these prediction errors were tied to activity in parts of the brain that are very important for learning and valuation. And we could infer how people felt about themselves before they actually reported on how they felt. And we identified a signal in the ventral medial prefrontal cortex that sort of keeps track of how good you feel about yourself.
Chris - So is that where you see this going next? You now have this objective data showing our self-esteem centre in the prefrontal cortex. Could you now take that forward and so will let's look at certain psychiatric illnesses or problems of esteem and depression and see how those illnesses and also getting better from those illnesses are reflected in the behavior of these brain regions.
Geert-Jahn - Yes, so that is exactly the direction that I'm going in. We are currently looking at how these processes might be different in people with levels of self-esteem that are much lower. And then the next step would be to study this in people who suffer from psychiatric disorders such as depression. Ultimately I hope that we can use these insights to design new treatments or design new methods for diagnosis.
12:29 - Salmon speed up sperm
Salmon speed up sperm
with Patrice Rosegrave, Otago University, & Michael Bartlett, University of Canterbury
When animals compete for mates it’s usually the largest, strongest specimens that are successful and drive off the competition. But the underdog may have a hidden hand to play. Working on Chinook Salmon, Michael Bartlett and Patrice Rosengrave have found that less dominant males can compensate for being lower down the social pecking order by adding something to their seminal fluid that dramatically accelerates their sperm and boosts their chances of reproductive success…
Michael - We know from previous research that when males compete in order to be successful in reproduction and have offspring they are able to make these really rapid adjustments to their ejaculates in terms of the number of sperm they might produce or how fast those sperm are able to swim. What we don't know is how they're able to make these adjustments particularly over such rapid time frames so faster than they're able to make new sperm for example.
Chris - That sounds extraordinary that the animals can actually change the behaviour of their sperm in response to the social milieu. So Patrice, How did you actually pursue this because this is not, this is pretty tricky to try and get to the bottom of whats going on here I would think.
Patrice - So we wanted to do was we manipulated the social status of the fish. We caught the fish that were returning upstream to spawn. We paired up the fish of equal size and we placed them in this confined Raceway. So then we wanted to observe the behaviour of the fish so we got a GoPro camera and we were able to make behavioral observations to determine which fish was the most dominant. We then placed the dominant male with the dominant male, and then the subdominant male with the subdominant male we measured their spare motility and we counted how many sperm cells they had.
Chris - Michael, when you do this, is this reflected in the sperm that you recover from the animals? Does that change in the way you would predict based on these observations showing that the social cues are affecting the behaviour of the sperm?
Michael - Yes when a male is dominant in status and then changes to subdominant status so the risk that sperm competition is higher, we see an increase in sperm velocity in those males.
Chris - And Patrice, have you got any idea as to how they're doing this because the changes are so rapid that they're not just making new super sperm de novo, they're physically changing the behaviour of their existing sperm aren't they.
Patrice - Yeah exactly. So what we think is there's some component of the seminal fluid that is upregulating sperm function. That's what we now need to explore what is in the seminal fluid, is it a protein, is it an enzyme that interacts to manipulate sperm function.
Chris - Could you get at that Michael, by say taking sperm from a dominant male, filtering out the cells so you have just the seminal fluid and adding that to the sperm of a less dominant animal and seeing if he gets a fertility boost or vice versa, accordingly.
Michael - Yes and so that was kind of the next stage in our experiment. We took sperm cells from dominant males and subdominant males and we recombine them in the seminal fluid of males of the other status. And what we saw was that when you put sperm cells from a dominant male into the seminal fluid of a subdominant male you see an increase in sperm velocity on average and the opposite effect when you take sperm from subdominant male which generally has faster sperm, We see that you get a decrease in sperm velocity when they're incubated in the seminal fluid of a dominant male.
Chris - One would infer then Patrice that there's something which is secreted into the seminal fluid in response to the fish's perception of how threatened or how dominant it is or isn't. And that is having this enlivening effect on the sperm. Is it reflected in fertilisation success though, if you take that enlivened, accelerated sperm does it have a greater prospect of fertilising eggs.
Patrice - Yeah that's exactly right. So we found that the subdominant males that had seminal fluid that sped up sperm, we found that if we added that to the dominant male sperm it also increased their fertilisation success so yeah you're exactly correct that there was a fitness effect.
Chris - So what do you think the implications of this are?
Michael - I would say that the seminal fluid the idea that it's implicated in this process has been floated for some time but we've lacked, kind of, experimental evidence showing that that's the case. So what we've done here is been able to provide evidence that really shows that seminal fluid is involved. Now what we really need are investigations looking at seminal fluid composition and then some kind of experimental work that links the component of seminal fluid to sperm function.
Chris - Patrice is there any effect on the female as well because is it just the sperm cells that respond to this admixture of whatever goes into the seminal fluid or is there the possibility that when the sperm actually come to do the job of doing the fertilisation they are enhanced beyond just what the sperm can do.
Patrice - Right. It's a really good question. We're not quite sure yet. So the eggs are the female have this fluid also around them called ovarian fluid. We're not quite sure yet how seminal fluid might interact with that fluid around the eggs. But there is a possibility that there could be an interaction between those two fluids and that could certainly influence sperm behaviour and potentially competitiveness between the sperm of different males.
17:50 - Biological existential risks
Biological existential risks
with Christian Boehm, University of Cambridge
Researchers at the Centre for the study of existential risk, in Cambridge, given the rapid pace at which sciences like molecular biology are advancing, set out to identify the leading biological threats we are likely to face in the near future. Christian Boehm is one of the authors of the new report...
Christian - Basically what the Center for the Study of extension risk have done this in the previous year bring together an internationally renowned team of 27 experts in biological engineering in order to identify future trends in the field which fulfil three criteria, in essence. And these three criteria: First, the issue needed to be considered emerging but not widely known beyond a specialist field. Secondly, the issue needed to be scientifically plausible. And third, the issue needed to be of potential global impact and so we started off with a long list of 70 potential emerging issues and use a structured and iterative approach to narrow down to the 20 which we outline in more detail in the final report.
Chris - And just briefly can you pick on some of those 20 and tell us why they made it to that shortlist and give us a flavour of, of why they deserve to be there.
Christian - Unfortunately I may not have the time to talk about all the 20 issues in detail but there were some overarching themes if you will, which touched upon several of these issues and one of those that I am particularly excited about is a shift in the nature of biology from a natural science towards an information science. And this has to do with the fact that the costs of sequencing and synthesis of DNA is falling rapidly. Since 2003 the cost of sequencing DNA has come down a million fold and that means that the intrinsic value of any DNA sequence, primary not any more lies in a physical sample of the organism was derived from but rather in the information about the function this fragment of DNA has or the product it encodes. This has a variety of implications for both academic research and the future of our economy.
Chris - And so what do you advocate? Given that dramatic landscape shift, what are you saying we should do instead?
Christian -Well with respect to cyber-biosecurity which I think will be an emerging subdiscipline in biological engineering, it will become increasingly important to protect digital biological sequence information and several strategies for managing these risks. One could consider, first the implementation of industry-wide standards for information security. Secondly, potentially the recognition of public sequenced databases as critical infrastructure. And third, the collaboration with information technology experts when developing new biotechnology tools and services.
Chris - So having highlighted these particular priorities where do you hope this will take you next?
Christian - Our horizon scanning exercise was just a first step. Because of the broad nature of the issues which have touched upon covering issues relevant to health, food supply, energy, but also access ownership, benefit sharing, and many more there really should be follow up exercises, ideally in collaboration with policymakers to prioritize the most actionable items and explore them in more detail to then hopefully come to a fruitful collaboration between scientists and policymakers.
Chris - Many of the things that you've highlighted in the manuscript though, they're pretty big problems. You've mentioned things relevant to say, climate change and that kind of thing which already have a lot of attention focused on them. So to what extent is this highlighting new concerns, and to what extent is it just sort of cheerleading saying "yes we really do need to worry about these things that we know are important."
Christian - Well of course especially the issues which become relevant in the near term. That is approximately the next five years, may be well known generally speaking such as we're all well aware that climate change may impose a substantial threat to humanity, or that we need to substantially boost our food production in order to feed up to 9 billion people 'til 2050. But this report will highlight specific technologies and developments within biological engineering such as artificial photosynthesis or the genetic engineering of chloroplasts which will likely make a difference in addressing these problems.
22:49 - A new genus of extinct horse
A new genus of extinct horse
with Peter Heintzman, Tromso University Museum
Horses, zebras, asses and donkeys are all members of the group, or genus, called “Equus”. Their first ancestors arose millions of years ago. But as recently as a few tens of thousands of years ago there were two anatomically quite different groups of these animals alive side by side on Earth. One group - called the stout-legged horses - are a close genetic match for all of the surviving horses around today. But the other group - called the stilt-legged horses - has since disappeared although it had a similar leg bone structure to certain family members that are still around today. Based on the anatomical similarities, palaeontologists had previously suggested that the extinct horses were related to today’s surviving species. Now a much more comprehensive genetic analysis using fossil DNA from stilt-legged specimens suggests that, instead, these stilt-legged horses were an entirely separate genus, which Peter Heintzman and his colleagues are dubbing Harringtonhippus...
Peter - In North America during the Pleistocene around 225 to 12000 years ago there were two groups of horses. One group that had these, kind of like, broad foot bone, stout foot bones which are very much like living horses and then there was this other group, the stilt-legged horses that had much more slender or thinner foot bones. In fact, these thinner foot bones that stilt-legged horses had were very similar to those of living Asiatic asses. Kiangs, Onagers, and Kulans which are relatives of donkeys and currently live in parts of Asia such as Tibet. However previous ancient DNA had shown that actually, they looked more like these stout-legged horses so like actually living horses. So we had these, kind of, competing ideas as to whether the stilt-legged horses were closely related to the living Asiatic asses or living horses.
Chris - Horses go back a long while though don't they, I mean they've been on Earth for what? More than 50 million years?
Peter - Yes, so the original ancestor of the horse lineage, so that includes living's zebras and donkeys, goes way back to around 55 million years ago to a very small animal called Hyracotherium, which was about the size of a dog. It had three toes instead of one and was a browser rather than a grazer. So it would eat leaves rather than grasses. Throughout the 55 million year history of horses in zebras and their relatives, they got larger, they lost two of their toes so they only have one toe now, and they generally became grazers but they didn't evolve in a linear fashion like that, there were many offshoots and extinct lineages now completely dead.
Chris - So how do you think we ended up in this situation about a hundred thousand years ago or so where you saw this these two groups living side by side with quite different foot structures then?
Peter - What we can do is infer from living horses and these Asiatic asses as to what they were potentially used for. So the Asiatic asses which have these similar foot structures to the stilt-legged horses live in very dry and quite inhospitable conditions today, so like on the Tibetan plateau. So it's likely that these stilt-legged horses based on these but these kind of like bone dimensions were living in quite dry and harsh environments.
Chris - So how did you seek to resolve some of these questions about where these animals came from and where they went?
Peter - We wanted to build on the previous ancient DNA findings that stilt-legged horses were quite closely related to living horses, and what we did is we generated a lot more data than have been generated before so we looked at more individuals and we generated whole mitochondrial genomes. So the mitochondria are these powerhouses that are in cells and they have their own genomes that are independent from the nuclear genome. So the main genome that's found inside living cells. And in addition to these mitochondrial genomes we also generated information from the nuclear genome and in the past people had only used the mitochondria before. And when we took all of that new data together we actually found something very interesting that the stilt-legged horse was actually very very different from living horses and actually from the Asiatic asses.
Chris - So where did it come from?
Peter - What we actually found is that it was so different that it fell completely outside of living horse diversity. So it seems that the lineage leading to the stilt-legged horses and that leading to modern horses, zebras, and donkeys diverged around 4 to 6 million years ago most likely in North America.
Chris - So it's a bit like what we see with early human ancestors where Nature was doing all these experiments in parallel with lots of different ancestors all coexisting and sitting side by side and slowly emerging from that are effectively the fittest and the best specimens. So you're saying you've got evidence you have a completely new genus which is sitting side by side, or running round side by side with what ultimately became modern surviving horses but these ones have gone.
Peter - Yes absolutely. So actually the genus Equus which living horses belong to, they also have a lot of extinct relatives but this new genus which we called Harringtonhippus, it became extinct around 14000 years ago in North America.
Chris - Any idea why it disappeared?
Peter - We don't know for sure, but what is intriguing is that it went extinct around the same time that Sabertooth Cats and Woolly Mammoths were going extinct. So it may be that there was a common cause to that.
Chris - Just thinking about what might have been happening then, we had an end of an Ice Age around that time. We also had a lot of human migration coinciding with that so they could be both climatological, but there could also be a mankind kind of blame.
Peter - Absolutely. These are kind of like, two very competing ideas at the moment. Whether, yeah, a lot of these extinctions were caused by climatic changes or by human overhunting or a mixture of the two. At this point in the case of the stilt-legged horse, it's a little too early to be able to answer that. But from other taxa it seems like human hunting probably exacerbated a problem that was caused by rapid climate warming that was occurring at the end of the last ice age.