Death sentence

30 April 2017

Interview with 

Colleen Murphy, Princeton University



Nematode worms use a pheromone to kiSome species exist as hermaphrodites, which means that a single organism can be both functionally male and female at the same time. In the case of the nematode worm C. elegans, though, it’s also useful from time to time to be able to produce offspring that are exclusively male. This is because they can mate with other hermaphrodites to boost genetic diversity. But then you don’t want too many males, because when they mate they shorten the lifespans of their partners, and you don’t want them hanging around competing for resources for longer than they’re needed; so how do you get rid of them? Colleen Murphy has discovered the answer - they kill themselves off with a pheromone to which only males are sensitive, as Chris Smith found out...

Colleen - The species, they are what are called hermaphrodites. So the mothers make their sperm and oocyte so they don’t need males. They only use males in times of stress when for example there are conditions where they might want to increase their genetic diversity by crossing. So they want to produce a lot of males in those cases. When those males mate with the mothers, then 50 percent of their progeny will be male and 50 percent will be female so you have these basically bursts of male production. The hermaphrodites turn out to want to get rid of those males. We discovered they have a very clever way of doing that which is the males themselves produce a pheromone that is actually toxic to themselves.

Chris - So you get this boom and bust population situation. There is genetic and there is environmental pressure to increase the number of males when you want to drive diversity, but at the same time, you don’t want that running out of control. So you hardwire into the system a death programme so that as the density of males goes up, they're secreting this pheromone that kills other males. So they will bring about their own demise.

Colleen - Exactly. It’s a very clever way I think of the hermaphrodites being able to say, “Well, we have these males. They need to be around for a while.” But they're actually going to kill themselves by making this dose-dependent toxic compound. And that will eventually drive the population of the males back down so that resumes the mostly hermaphroditic population.

Chris - How do the males detect that pheromone in the environment then?

Colleen - We assume there's three receptors although the receptor for that male pheromone, I don’t believe is known yet. We certainly don’t know it and we don’t know which neurons detect it, but we know that neurons are involved in this. There's a genetic trick where you can make the neurons of those hermaphrodites males. When we did that experiment, those hermaphrodites both produced the male pheromone and they received male pheromone as a toxin.

Chris - Now, when a male mates with a hermaphrodite, that also has a negative effect on the hermaphrodite. Is it bypassing the neurological detection? Is it the same death signal but it’s just getting in via a different route or is that a totally independent mechanism?

Colleen - That seems to be an independent mechanism. We’ve been able to find that those are due to the transfer of sperm and seminal fluid just by using genetic tricks where the males don’t make either of those but they still make a pheromone. The pheromone in that case doesn’t affect the female. It’s really the presence of this germline ramping up of activity from the sperm and unidentified components in the seminal fluid that makes their hermaphrodite die early.

Chris - Have you contemplated doing the experiment where you just stop them being able to kill off these males like this and then just grow generations of them and see what happens to population fitness, population numbers, and so on?

Colleen - So we’ve dreamed about a lot of these types of experiments. In our hands, it’s been very difficult. These animals have at least 300 progeny each and they have about a thousand if they mate and they quickly grow out of control. So, there are lots of thought experiments that we’ve mulled over but we haven't actually carried out any multigenerational – at least not successfully. We’ve done a lot of modelling to try to figure out, what would happen if you just, for example, inhibit their ability to be fertile or produce progeny, and that’s how we were able to show that prediction would be that they'd go back to mostly hermaphroditic species after several generations. Certainly losing it, we haven't thought so much about that. We’re really mostly interested in trying to figure out the mechanism that’s at work there now. What is the mechanism by which they actually kill the animals because it doesn’t look like any of the other lifespan or longevity pathways we’ve worked on previously?


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