Investigating the consequences of the mating system for drug resistance evolution inC. elegans
Authors: Trubenová B. , Hellinga J. , Krücken J. , von Samson-Himmelstjerna G. , Schulenburg H. , Regoes R. 
Published: November 2024

Helminth infections, a significant global health concern, are effectively treated with anthelmintic drugs. However, the rise of anthelmintic-resistant strains in livestock threatens both animal and human health. Understanding the factors influencing anthelmintic resistance is crucial to mitigate the threat posed by these parasites. Due to difficulties in studying parasitic worms in the laboratory, the non-parasitic nematodeCaenorhabditis elegansis used as a model organism to investigate anthelmintic resistance evolution. However, the suitability of this free-living nematode as a model for parasitic worms is also debatable due to its unique androdioecious reproductive mode, which enables hermaphrodites to reproduce by selfing or mating with males. While selfing offers efficient selection and allows reproduction in the absence of mating partners, it can reduce genetic diversity and lead to the accumulation of harmful mutations. On the other hand, selfing can also expose beneficial resistance mutations, speeding up adaptation. Conversely, outcrossing with males introduces new genetic variation, aiding adaptation but potentially slowing the spread of beneficial mutations. The androdioecious reproductive system is rare among nematodes, raising questions about the generalizability of findings from evolutionary experiments inC. elegansto other species with different mating systems. In this study, we aim to evaluate and improve the suitability ofC. elegansas a model organism for investigating the evolution of anthelmintic resistance in parasitic nematodes. We developed a polygenic model incorporating various reproductive modes and drug resistance to better understand the complex interplay between reproductive mode and resistance evolution. Combining a population genetic perspective on anthelmintic resistance evolution with pharmacodynamic modelling, we investigated the effects of reproductive strategy and other aspects, such as dominance, mutational effects, the number of loci, and population size, in determining the dynamics and outcome of evolutionary processes. We found that androdioecious populations exhibited rapid initial adaptation, typical for hermaphrodites, alongside the ability to endure high drug concentrations, which was observed in dioecious populations. Androdioecious populations also exhibited the highest diversity and shortest time to fixation of the beneficial allele. These results suggest that androdioecious populations can harness the advantages of both selfing and outcrossing, optimizing their reproductive strategy in response to drug selection. Both population size and the specific genetic architecture of resistance influence the ideal balance between these reproductive modes. By enhancing our understanding of how reproductive modes shape the development of antibiotic resistance, we believe our findings will help us utilizeC. elegansmore effectively as a model for studying parasitic nematodes, which are typically dioecious.