Phenotypic and transcriptomic similarity between the N2 Ancestral and a Tropical wild isolate of C. elegans reveals divergence from the reference Bristol strain

In recent years, the scientific community has increasingly recognized the importance of incorporating ecologically relevant perspectives into laboratory research. In the case of the free-living nematode Caenorhabditis elegans, numerous studies have documented the domestication of the N2 Bristol strain (isolated in 1951). This has led to a growing interest in recently isolated wild strains from diverse latitudes, which offer insights into natural variation evolution and life-history traits. Here, we compared a recently isolated tropical strain from Mexico City to the N2 Bristol strain. To contextualize laboratory adaptation, we also included the N2 Ancestral strain, a cryopreserved lineage from 1969 with minimal generational drift. Phenotypic assays revealed that, under standard laboratory conditions, the Mexican strain exhibited reduced lifespan and fertility, but enhanced resistance to Pseudomonas aeruginosa, whereas the Ancestral strain showed higher oxidative stress tolerance but reduced thermotolerance. RNA-seq analyses showed that transcriptomic profiles of the Mexican and Ancestral strains were more similar to each other than to the N2 Bristol, suggesting that long-term domestication has driven regulatory divergence. Differential gene expression analyses identified strain-specific signatures in stress, immune and collagen-related pathways. Under heat stress, transcriptional profiling revealed that only a small set of canonical heat shock genes was commonly upregulated across the three strains, yet wild strains showed more dynamic regulation, while N2 Bristol exhibited a distinct, possible preconditioned response. These findings reveal phenotypic trade-offs and regulatory divergence shaped by natural versus laboratory environments, and underscore evolutionary dynamics and adaptive potential of C. elegans in response to distinct ecological histories.