A role for worm cutl-24 in background- and parent-of-origin-dependent ER stress resistance.

BACKGROUND: Organisms in the wild can acquire disease- and stress-resistance traits that outstrip the programs endogenous to humans. Finding the molecular basis of such natural resistance characters is a key goal of evolutionary genetics. Standard statistical-genetic methods toward this end can perform poorly in organismal systems that lack high rates of meiotic recombination, like Caenorhabditis worms. RESULTS: Here we discovered unique ER stress resistance in a wild Kenyan C. elegans isolate, which in inter-strain crosses was passed by hermaphrodite mothers to hybrid offspring. We developed an unbiased version of the reciprocal hemizygosity test, RH-seq, to explore the genetics of this parent-of-origin-dependent phenotype. Among top-scoring gene candidates from a partial-coverage RH-seq screen, we focused on the neuronally-expressed, cuticlin-like gene cutl-24 for validation. In gene-disruption and controlled crossing experiments, we found that cutl-24 was required in Kenyan hermaphrodite mothers for ER stress tolerance in their inter-strain hybrid offspring; cutl-24 was also a contributor to the trait in purebred backgrounds. CONCLUSIONS: These data establish the Kenyan strain allele of cutl-24 as a determinant of a natural stress-resistant state, and they set a precedent for the dissection of natural trait diversity in invertebrate animals without the need for a panel of meiotic recombinants.

Cold Survival and Its Molecular Mechanisms in a Locally Adapted Nematode Population.

Since Darwin, evolutionary biologists have sought to understand the drivers and mechanisms of natural trait diversity. The field advances toward this goal with the discovery of phenotypes that vary in the wild, their relationship to ecology, and their underlying genes. Here, we established resistance to extreme low temperature in the free-living nematode Caenorhabditis briggsae as an ecological and evolutionary model system. We found that C. briggsae strains of temperate origin were strikingly more cold-resistant than those isolated from tropical localities. Transcriptional profiling revealed expression patterns unique to the resistant temperate ecotype, including dozens of genes expressed at high levels even after multiple days of cold-induced physiological slowdown. Mutational analysis validated a role in cold resistance for seven such genes. These findings highlight a candidate case of robust, genetically complex adaptation in an emerging model nematode, and shed light on the mechanisms at play.