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

Area of Science:

• Genetics and Molecular Biology
• Developmental Biology
• Systems Biology

Background:

• Complex traits and diseases involve multiple genes acting in various pathways.
• Signalling pathways like apoptosis, MAPK, Notch, and Wnt are crucial for development and disease.
• Understanding how genetic variations affect gene expression at the translational level is limited.

Purpose of the Study:

• To investigate the impact of natural genetic variation on transcript and protein abundance in key developmental signalling pathways.
• To identify quantitative trait loci (QTLs) associated with protein abundance variations.
• To link genetic variation to phenotypic changes in signaling pathways.

Main Methods:

• Utilized recombinant inbred lines (RILs) from contrasting wild-type Caenorhabditis elegans strains (N2 and CB4856).
• Employed selected reaction monitoring (SRM) mass spectrometry to quantify protein abundance in four key pathways.
• Performed quantitative trait locus (QTL) mapping to identify genetic loci influencing protein levels.

Main Results:

• Approximately 50% of the 44 tested genes showed statistically significant changes in protein abundance across different strains, though most changes were minor (<1.3-fold).
• Identified a QTL on chromosome II affecting the abundance of the phosphatidylserine receptor protein (PSR-1).
• Detected two distinct QTLs on chromosome IV associated with embryonic and radiation-induced apoptosis.

Conclusions:

• Natural genetic variation in C. elegans is sufficient to induce significant alterations in developmental signalling pathways.
• These variations affect both gene expression (transcript and protein levels) and observable phenotypes.
• The study provides insights into the genetic basis of complex traits and disease-related pathways.