Genomic Analysis of QTLs and Genes Altering Natural Variation in Stochastic Noise

Abstract

Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic loci are distributed within the genome. Understanding these questions is critical to our understanding of quantitative traits and how they relate to the underlying causal loci, especially since stochastic noise may be directly influenced by underlying changes in the wiring of regulatory networks. We identified QTLs controlling natural variation in stochastic noise of glucosinolates, plant defense metabolites, as well as QTLs for stochastic noise of related transcripts. These loci included stochastic noise QTLs unique for either transcript or metabolite variation. Validation of these loci showed that genetic polymorphism within the regulatory network alters stochastic noise independent of effects on corresponding average levels. We examined this phenomenon more globally, using transcriptomic datasets, and found that the Arabidopsis transcriptome exhibits significant, heritable differences in stochastic noise. Further analysis allowed us to identify QTLs that control genomic stochastic noise. Some genomic QTL were in common with those altering average transcript abundance, while others were unique to stochastic noise. Using a single isogenic population, we confirmed that natural variation at ELF3 alters stochastic noise in the circadian clock and metabolism. Since polymorphisms controlling stochastic noise in genomic phenotypes exist within wild germplasm for naturally selected phenotypes, this suggests that analysis of Arabidopsis evolution should account for genetic control of stochastic variance and average phenotypes. It remains to be determined if natural genetic variation controlling stochasticity is equally distributed across the genomes of other multi-cellular eukaryotes.

Canalization of Tomato Fruit Metabolism

“…The high-resolution nature of the BILs, along with the fact that the genomes of both parental lines have been sequenced (Bolger et al, 2014), rendered it possible to obtain relatively short gene lists for the nine regions that we used for validation via the independent population (Supplemental Data Set 14). Interestingly, several of the genes contained within the cross-validated intervals are associated with regulatory proteins, including those encoding chaperones, receptor-like kinases, and transcription factors (see Supplemental Files 1 and 2 for a detailed discussion) and as such are similar to previously described genes associated with canalization of developmental phenotypes in both plants (Queitsch et al, 2002;Hall et al, 2007;Jimenez-Gomez et al, 2011) and other biological systems (Rutherford and Lindquist, 1998;Specchia et al, 2010).…”

Additive, Epistatic, and Environmental Effects Through the Lens of Expression Variability QTL in a Twin Cohort

“…There is empirical evidence across several species that the variance among phenotypes is genotype dependent (Ansel et al 2008;Wolc et al 2009;Hill and Mulder 2010;Jimenez-Gomez et al 2011). Understanding genetic control of phenotypic variability has become increasingly important in evolutionary biology, human medicine, the agricultural industry and other branches of biological science (Gibson 2009;Yang et al 2012).…”

Heritable Environmental Variance Causes Nonlinear Relationships Between Traits: Application to Birth Weight and Stillbirth of Pigs

“…There are more recent data on genetic control of V E at the level of individual loci from genome-wide association studies (see review by GeilerSamerotte et al 2013). Those in experimental species are very clear cut: for example, Jimenez-Gomez et al (2011) and Nelson et al (2013) located QTL for phenotypic variability in gene expression in Arabidopsis and yeast, respectively, and Shen et al (2012) identified regions controlling the phenotypic variability of traits in Arabidopsis. In vertebrates, the FTO genotype was shown to be associated with phenotypic variability in body mass index in humans, with the two homozygotes differing 7% in standard deviation (SD) (Yang et al 2012).…”