Mapping Determinants of Gene Expression Plasticity by Genetical Genomics in C. elegans

Abstract

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 °C and 24 °C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 °C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity. It is widely documented that environmental changes will induce differential expression of genes, yet it is unknown how these patterns of environment-induced expression plasticity are inherited and how they differ between genetically divergent individuals of a biological species. In this paper the authors used recombinant inbred lines of the nematode worm C. elegans that were derived from parental lines originally collected in Bristol (United Kingdom) and Hawaii, and measured genome-wide gene expression at two different temperatures. Using statistical analysis tools developed for quantitative trait locus mapping, they found genes with genetically determined differences in their plastic response to temperature changes. A majority of them were found to be regulated by genes at a different genome position (regulated in trans). A striking observation was a group of 66 genes that share a common potential regulator and may be related to differences in fertility plasticity. These results show that differential responses of different genotypes to environmental changes are widespread. Because all species are subjected to environmental change, both at individual and evolutionary time scales, the authors' work calls for studying the heritable component of plasticity of gene regulation in other organisms to enhance understanding of the environmental forces that drive evolutionary adaptation.