Research Article: Reimagining pheromone signalling in the model nematode Caenorhabditis elegans

Date Published: November 2, 2017

Publisher: Public Library of Science

Author(s): Mark Viney, Simon Harvey, Kaveh Ashrafi

Abstract: None

Partial Text: Caenorhabditis elegans is an important, widely used developmental and genetic model. A pheromone has long been known to cause juvenile developmental arrest in C. elegans, a phenomenon that is common among nematodes more widely. Many novel effects of this pheromone are now being discovered—most recently, that exogenous supply of this pheromone controls adult worms reproduction. Here, we suggest that to properly understand and interpret these phenomena, C. elegans natural ecology must be considered, about which rather little is known. With this perspective, we suggest that C. elegans pheromone signalling evolves very locally, such that there are different dialects of pheromone signalling among ecological communities and among kin groups, and we also argue that pheromone signals may also evolve to be manipulative and dishonest. New approaches must be undertaken to study these phenomena in C. elegans. While model systems have been tremendously important tools in modern biological research, taking account of their natural history is necessary, and key, to properly understand and interpret laboratory-based discoveries.

Dobzhansky’s dictum—that nothing in biology makes sense except in the light of evolution—has served biology well. But we would add to this that nothing observed of an organism in a laboratory makes sense except in the light of that organism’s natural history. This may not be a controversial statement—indeed, such calls have been made before [1–3]—but it is particularly apposite to a recent spurt of discoveries in the nematode worm C. elegans that, we suggest, require a critical reinterpretation in the light of the worm’s natural history. Specifically, new work is uncovering how C. elegans worms communicate with each other using a pheromone to affect each other’s reproduction [4]. Here, we suggest that properly understanding and interpreting these results requires an ecological perspective and that we therefore need to reevaluate how we study these phenomena in this important model organism. Beyond C. elegans, studies of other nematodes—the animal parasitic nematode Strongyloides ratti [5, 6] and the beetle-associated Pristionchus pacificus [7]—have considered these species’ ecology in interpreting laboratory-based results; it’s now time for the C. elegans field to do this too.

C. elegans is a free-living nematode. In its 3-day life cycle, offspring of adult worms moult through 4 larval stages (L1–L4) before moulting back into the adult stage. This life cycle is shared by most nematodes, including parasitic species, which are of enormous medical and agricultural importance. For C. elegans, its life cycle contains a development choice, in which an L3 stage can either continue (via an L4), growing into a reproductive adult, or can instead arrest development as an alternative L3 stage called a dauer larva. Dauer larvae have a specialised structure, physiology, and behaviour that allow them to persist in the environment for weeks. When environmental conditions improve, dauer larvae resume development, growing (via the L4 stage) into reproductive adults.

C. elegans pheromone plays a critical role in worms deciding whether or not to enter dauer larval arrest. It consists of a complex mixture of (apparently nematode-specific [11]) ascaroside molecules—ascarylose sugars attached to various side chains—but also includes some structural variants (such as indole ascarosides). There is also recent evidence of yet other types of molecules too [4, 12, 13]. This suite of ascaroside molecules is a modular library, with the module components deriving from peroxisomal β-oxidation of fatty acids, carbohydrate metabolism, and amino acid catabolism [12, 14]. All told, some 150 different ascaroside molecules have so far been identified in C. elegans pheromone (with some 200 known from over 20 different nematode species more generally) [11, 12], thereby revealing this pheromone’s substantial complexity.

The original role ascribed to C. elegans pheromone was inducing the development of dauer larvae, but now an increasingly diverse set of roles have been (and continue to be) discovered for it. For example, pheromone acts as a chemoattractant between adult males and adult hermaphrodite worms [13, 20], and it promotes aggregation of worms [10] and foraging behaviour [18]. Exogenously supplied pheromone can also increase adult lifespan and fecundity and accelerate hermaphrodite development and the maintenance of their germline precursor cells [4, 23–25]. Worms’ response to pheromone is also condition dependent, with the progeny of poorly fed mothers less likely to develop into dauer larvae in response to exogenous pheromone [26]. Collectively, these results are therefore revealing how C. elegans pheromone can affect multiple (perhaps all) life cycle stages and that it can also have major effects on adult reproduction. Moreover, these effects will all act to change the population dynamics of C. elegans.

Our understanding of C. elegans natural ecology is embarrassingly slim [27], especially in comparison with the exquisite detail with which we understand elements of its anatomy, cell biology, and genetics. It lives in ephemeral habitats, principally rotting vegetation (though it is also found on molluscs and arthropods [28–32]), where there are likely extended periods when there is no food and then relatively short-lived periods of abundant food. The dauer stage allows worms to persist in food-depleted environments; that the dauer stage is very commonly found in the environment [8–10] is testament to the frequency with which there is insufficient food available. When food is available, adults rapidly exploit it to reproduce. Wild populations are probably relatively small, with dauer larvae being common in populations of tens of thousands of worms (which could be due to only a few generations of reproduction), suggesting that this may be the maximum size to which a local population can grow [33, 34]. C. elegans shows significant population genetic differentiation among sample locations [35], with the abundance of different genotypes slowly changing over time [36].

We suggest 3 different, but interrelated, hypotheses concerning C. elegans pheromone signalling in the wild.

In summary, we suggest that C. elegans pheromone signalling acts and evolves in ecological communities, including kin groups, which may drive the development of community-specific pheromone signalling, including private among-kin signalling as well as signalling that is not always honest.