Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains Bristol N2 and Hawaii CB4856 to enable quantitative trait loci (QTL) mapping. Variation in gene expression was greater in the RILs than in the parental lines, at the proteome as well as at the transcriptome levels. We detected a trans-QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels. Parental genotypes N2 (3x) and CB4856 (3x) and 47 RILs from (Li etal 2006; Vinuela etal 2010 and Elvin etal 2011)