The team combines evolutionary, ecological and quantitative approaches to the biology of a major model organism, the nematode worm Caenorhabditis elegans. Biological processes are generally studied in the laboratory under one environmental condition and in one reference genetic background. Instead, we study a biological system in its evolutionary context, focusing on C. elegans vulval cell fate patterning and its robustness, evolution and evolvability. In order to develop an evolutionary and ecological framework for this model organism, we started to isolate and study natural populations of C. elegans and relatives, especially they’re out crossing rate, population structure and ecology. We study their co-evolution with natural pathogens, especially recently discovered viruses.
One main focus of the team is the evolution of a key model system in developmental genetics, nematode vulva development.
The robustness of the vulval cell fate patterning system was measured in different environments for several wild isolates of C. elegans and C. briggsae. The relative frequencies of different cell fate pattern variants point to a differential sensitivity of the developmental mechanisms behind the corresponding variants. For example, the most variable vulval development trait is highly sensitive to gene dosage of two long-range Wnt signals.
Using mutation accumulation lines started from different wild genetic backgrounds, we measured the capacity to evolve (=mutational variance, evolvability) of different vulva characters. We compared this evolvability in the absence of selection to natural variation, thus deducing the effect of selection. Different vulval characters display widely different evolvabilities, which partly correlate with their evolutionary rate of change. This relative evolvability itself evolves, which may partly explain observed biased patterns of evolutionary variation (evolutionary trends) within and between closely related species. These results have strong implications concerning the respective roles of mutational bias versus natural selection in phenotypic evolution.
Whereas the final pattern of vulva precursor cell fates is quite robust and invariant, the underlying developmental mechanisms vary quantitatively depending on genetic background and environment. Such cryptic evolution of developmental mechanisms was found at micro- and macro-evolutionary scales. We developed a computational model of the known vulva molecular signaling network and could localize different Caenorhabditis species in system parameter space.
The second focus of the team concerns Caenorhabditis natural population studies. We could efficiently isolate Caenorhabditis species, study their habitats, discover many new Caenorhabditis species and determine C. elegans genetic population structure (spatial structure, outcrossing rate). Several natural pathogens of C. elegans were isolated, including microsporidia, bacteria, fungi and recently the first viruses that infect C. elegans or C. briggsae, which will be relevant to study defense systems and their rapid evolution.
Nematode strain collection of the team: http://www.justbio.com/worms/index.php
Barkoulas, M., van Zon, J.S., Milloz, J., van Oudenaarden, A., Félix, M.-A. Robustness and epistasis in the C. elegans vulval signalling network revealed by pathway dosage modulation. Developmental Cell (2013). 24, 64-75.
Ashe, A., Bélicard, T., Le Pen, J., Sarkies, P., Frézal, L., Lehrbach, N.J., Félix, M.-A., Miska, E.A. A deletion polymorphism in the C. elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. eLife (2013). 2:e00994.
Duveau, F. and Félix, M.-A. Role of pleiotropy in the evolution of a cryptic developmental variation in C. elegans. PLoS Biology (2012). 10, e1001230.
Hoyos, E., Kim, K., Milloz, J., Barkoulas, M., Pénigault, J.-B., Munro, E. and Félix, M.-A. Quantitative variation in autocrine signaling and pathway crosstalk in the Caenorhabditis vulva network. Current Biology (2011). 21, 527-538.
Félix, M.-A., Ashe, A., Piffaretti, P., Wu, G., Nuez, I., Bélicard, T., Jiang, Y., Zhao, G., Franz, C.J., Goldstein, L.D., Sanroman, M., Miska, E.A., Wang D. Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS Biology (2011). 9, e1000586.