The quantitative genetics of gene expression in Mimulus guttatus

Abstract

Gene expression can be influenced by genetic variants that are closely linked to the expressed gene (cis eQTLs) and variants in other parts of the genome (trans eQTLs). We created a multiparental mapping population by sampling genotypes from a single natural population ofMimulus guttatusand scored gene expression in the leaves of 1,588 plants. We find that nearly every measured gene exhibits cis regulatory variation (91% have FDR < 0.05) and that cis eQTLs are usually allelic series with three or more functionally distinct alleles. The cis locus explains about two thirds of the standing genetic variance (on average) but varies among genes and tends to be greatest when there is high indel variation in the upstream regulatory region and high nucleotide diversity in the coding sequence. Despite mapping over 10,000 trans eQTL / affected gene pairs, most of the genetic variance generated by trans acting loci remains unexplained. This implies a large reservoir of trans acting genes with subtle or diffuse effects. Mapped trans eQTLs show lower allelic diversity but much higher genetic dominance than cis eQTLs. Several analyses also indicate that trans eQTL make a substantial contribution to the genetic correlations in expression among different genes. They may thus be essential determinants of “gene expression modules”, which has important implications for the evolution of gene expression and also how it is studied by geneticists.Author summaryMimulus guttatus (yellow monkeyflower) is a model for the study of quantitative trait evolution in natural populations. Research has focused mainly on whole organism traits like flower size or herbivore resistance, but the level of expression of a gene is also a quantitative trait. In this study, we dissect leaf transcriptome variation using a breeding design that estimates the contribution of individual loci to expression variation (eQTLs). We find at least rough agreement to the “oligogenic model” where a major locus (the cis regulatory region) generates much of the genetic variation in the population. While associations studies routinely characterize genetic effects as binary (the two alternatives at a single nucleotide polymorphism or “SNP”), this description proves insufficient for Mimulus. Most loci exhibit multiple, and in some cases, a continuum of alleles. We find that trans eQTLs have different features than cis eQTLs, both in terms of the diversity and genetic dominance of alleles. These genetic features of eQTLs are critical determinants of the “G matrix”, the genetic variances and covariances among all genes. The G matrix determines how gene expression will evolve under selection in response to changing environmental conditions. Our finding of large effect sizes and high allelic diversity suggests that the G matrix may be surprisingly malleable, even on ecological timescales.