Selection at linked sites shapes heritable phenotypic variation in C. elegans

Abstract

Mutation generates the heritable variation that genetic drift and natural selection shape. In classical quantitative genetic models, drift is a function of the effective population size and acts uniformly across traits, whereas mutation and selection act trait-specifically. We identified thousands of quantitative trait loci (QTLs) influencing transcript abundance traits in a cross of two Caenorhabditis elegans strains; although trait-specific mutation and selection explained some of the observed pattern of QTL distribution, the pattern was better explained by trait-independent variation in the intensity of selection on linked sites. Our results suggest that traits in C. elegans exhibit different levels of variation less because of their own attributes than because of differences in the effective population sizes of the genomic regions harboring their underlying loci.

Figure 1

A. QTLs for each transcript abundance phenotype, significant at a False Discovery Rate of 5%, are plotted in rows located at the genomic positions of the transcripts. Gray bars represent 1-lod support intervals. The diagonal includes local QTLs, those that co-localize with the transcript they affect. Three robust QTL hotspots are indicated with arrows. B. Local lod score is plotted for each probe at its physical position along the chromosomes. Points in blue are significant at a 5% False Discovery Rate according to a single-marker linkage test. Points are scaled according to the fraction of variance in transcript abundance explained by the local QTL.

Figure 2

A. The significance of background selection in a logistic regression model (which includes gene-specific mutation and selection variables) is plotted as a function of the index of panmixis and strength of selection against deleterious mutations. Background selection is significant at p < 0.01 across all but a small slice of parameter space corresponding to very low rates of outcrossing (black). The red lines bracket the region of parameter space over which background selection explains more of the local linkage probability than any other variable in the model. See Figure S4. B. Effects of background selection on levels of variation along the chromosomes under the best fitting background selection model.