Abstract
A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address here this question by focusing on the epidermal seam cells, which display stem cell properties in Caenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is better tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces stem cell fate by acting through the Wnt pathway. Within one QTL region, genetic variation in the conserved heat shock protein HSP-110HSPA4 modulates egl-18 mutation expressivity. Our results highlight that natural variation in heat shock proteins can shape mutation expressivity influencing stem cell behaviour.
Competing Interest Statement
The authors have declared no competing interest.