Multiple interacting loci explain natural variation in C. elegans germ stem cell niche activity
Presentation
Overview
Overview
Description
A fundamental goal of evolutionary biology is to understand the divergence of genetic and developmental mechanisms underlying the great diversity of organismal life histories. Comparison among distant taxa cannot easily address this issue due to high complexity; however, it is possible to investigate the quantitative genetic architecture underlying life history and developmental phenotypes within species. Here we show that C. elegans wild isolates from around the globe display extensive size variation of the germline mitotic zone (MZ), indicative of variation in germline proliferative activity. To learn more about the molecular genetic differences underlying such natural variation in the C. elegans germ stem cell niche, we focused on two wild isolates, JU1200 and JU751, with strong differences in the size of total germline and mitotic compartment. Quantification of MZ size in ~70 F2 recombinant inbred lines (RILs) derived from the parental cross between these two isolates and subsequent quantitative trait locus (QTL) mapping identified a large-effect QTL on chromosome II (~7.25 Mb) that acts additively with a QTL on chromosome V (~2.6Mb). Together, these two loci explain ~32% of the observed phenotypic variation. While efforts to identify causal variants in the chromosome II QTL region were unsuccessful, we were able to investigate a promising candidate variant within the chromosome V QTL. Through CRISPR-Cas9 gene editing, we demonstrate that this variation, a 150bp INDEL upstream of lag-2 containing a BHLH-2 binding site, strongly affects MZ size in the JU1200 genetic background but not in the JU751 background, suggesting that there are other small effect loci in the genetic background important in determining MZ size. Together, our results identify a specific molecular variant affecting a cellular process that ultimately regulates reproductive potential, and they shed light on the complex, quantitative genetic architecture underlying natural variation in a germ stem cell niche.
