Institut de Biologie de l'École Normale Supérieure ENS . CNRS UMR8197 . Inserm U1024 Directeur : Pierre Paoletti

Evolution of Caenorhabditis

The team combines laboratory biology and eco-evolutionary approaches on a model organism, the nematode worm Caenorhabditis elegans.

While biological processes are generally studied in the laboratory within a single environment and genetic background, our approach is to place a biological system in evolutionary and environmental contexts. In other words, we integrate developmental and cell biology mechanisms with evolutionary biology.

Research Topics

• Evolutionary system biology: Quantitative evolution of an intercellular signaling network, experimental modulation and modeling, evolution of the genotype-phenotype map
• Quantitative genetics: Characterization and molecular identification of intraspecific genetic variation underlying the evolution in various phenotypes (development, immunity, reproduction).
• Evolutionary genomics: Monitoring of wild populations, structural polymorphsims and transposons
• Natural populations of Caenorhabditis: Habitat, new species, population structure and reproductive modes
• Host-parasite evolution: Microbes associated with Caenorhabditis species (virus, bacteria, microsporidia, etc.), coevolution of nematodes and their pathogens, evolution of small-RNA pathways
• Evolution of small RNA-mediated inheritance and germline immortality

Research Highlights

Quantitative studies of development and its variation

The team introduced quantitative studies of development on the vulva system of C. elegans, particularly to study its robustness and sensitivity to environmental or genetic perturbations and to quantitative modifications of signaling pathways.

They demonstrated the effect of environmental context and genetic background on the expressivity of mutations, placing in perspective the results of genetic screens obtained in a reference context.
A major finding concerns the evolution of signaling pathways specifying the vulval cells: while the final pattern of central cell fates is invariant, the team showed that the developmental route leading to it evolves between species and varies within a species depending on genetic background and environment - a key example of what has been called "developmental system drift". Different species of Caenorhabditis are located in the parameter space of a quantitative model of the signaling network.

Developmental bias and its effect in evolution

A major contribution concerns the evolutionary effect of the genotype-phenotype relationship: while mutations affect genes at random, they do not necessarily affect phenotypes at random. Using mutation accumulation lines started in different wild genetic backgrounds, the team measured the capacity to evolve (=mutational variance, evolvability) of the fates of the different vulval precursor cells. This evolvability itself evolves and corresponds to evolutionary trends observed across different genera and species.

The most variable developmental trait is highly sensitive to the gene dosage of long-range Wnt signals (represented highly schematically below).

The genotype–phenotype relationship, through development or any process shaping phenotypes, thus biases the distribution of phenotypes available to selection and affects their rate of evolution. This demonstrates the role of the genotype–phenotype relationship in evolutionary tendencies and explains them through differential sensitivity of developmental mechanisms. These results have strong implications for the respective roles of developmental bias and selection in evolution.

Natural populations

The team also "leaves the lab" to catch and study in the field natural populations of this model organism, whose natural habitat and lifestyle were previously unknown.

They discovered populations of C. elegans growing in decaying plant matter (fruits, flowers, stems). Identifying this habitat enabled the discovery of many variants of C. elegans and new species of the same genus, which have become the basis for diverse studies, particularly on speciation. Demographic data define a life cycle in nature for this model organism: C. elegans proliferates rapidly for several generations in a substrate, then migrates in a diapause stage to a new substrate, partly via vector animals.

The species reproduces through self-fertilization of hermaphrodites (XX) or facultative crossing with males (X0), which makes it a good model to study the effect of sexual reproduction. Other isolated nematodes show remarkable types of reproductive mode. The team monitors C. elegans populations near Paris and measures the nucleotide substitution rate in clonal populations over the years.

Associated organisms, particularly natural pathogens, are highly relevant to study the rapid evolution of immune defenses, the sensory system, and metabolism. During field campaigns around Paris and worldwide, the team isolated microsporidia, bacteria, fungi, oomycetes, and the first viruses of Caenorhabditis.

The discovery of the Orsay virus enabled the study of antiviral defenses in C. elegans, particularly the physiological role of small RNAs and polymorphisms in the immune system. These various collections now allow many laboratories to develop novel research lines.

Genetic variations in non-genetic inheritance mechanisms

The team discovered that a number of wild C. elegans strains display a multigenerational sterility phenomenon, and identified a DNA sequence polymorphism underlying the phenotype.

As this mortal germline phenotype is often the sign of a defect in small RNA inheritance, they tested and found that C. elegans strains show large variation in the presence and duration of gene silencing after an initial RNA interference trigger. Some do not inherit the silencing after the trigger is removed, while the others vary greatly in the number of generations of silencing. This demonstrates intraspecific variation in the duration of epigenetic inheritance. This result has implications concerning the evolution of unconventional heredity mechanisms and provides tools to study it.

Nematode strain collection of the team
World collections from several laboratories