Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans

Abstract

BackgroundCryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population.ResultsWe measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly shared across treatments. A considerable fraction of the trans-eQTL (40–57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL.ConclusionsThese results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 h) and that CGV is mainly determined by response related trans regulatory eQTL.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3899-8) contains supplementary material, which is available to authorized users.

Tensor Decomposition of Stimulated Monocyte and Macrophage Gene Expression Profiles Identifies Neurodegenerative Disease-specific Trans-eQTLs

“…Among the significant trans-eQTLs, we found 55% were stimuli-specific, suggesting that a larger number of trans-eQTLs are detectable only in the presence of specific stimuli. These observations are consistent with findings from other species such as Caenorhabditis elegans 37 and Saccharomyces cerevisiae 38 showing that environmental perturbation yields a higher number of trans-eQTLs compared to cis-eQTLs. Together, these results underscore the need to perturb primary cells with environmental stimuli to discover genotype-phenotype relationships in trans.…”

Genome structure predicts modular transcriptome responses to genetic and environmental conditions

“…Moreover, of differentially expressed genes affected by genotype, 32.6% have zero downstream SNPs, 20.3% have zero intronic SNPs, and 18.6% have zero SNPs in the coding sequence, also consistent with a major role of trans ‐regulatory control being responsible for the genotype dependence of differential expression. Consistent with this idea, C. elegans shows a predominant role of trans ‐regulatory control in genotype‐dependent differential expression to acute heat stress (Snoek et al, ).…”

“…In this context, extensive transcriptome analysis of the nematode Caenorhabditis elegans in response to heat shock and knock‐out mutation began with microarrays (Kim, Lund, & Kiraly, ), with more recent studies using recombinant inbred lines of wild strains to map polymorphic loci that contribute genotype‐dependent responses to temperature (Grishkevich et al, ; Li et al, ; Snoek et al, , ). For example, Li et al () found that among 496 detectable expression quantitative trait loci (eQTL), trans ‐eQTL were nearly eight times as likely as cis ‐eQTL to show genotype‐by‐temperature responses, with subsequent study reinforcing this pattern (Snoek et al, ). Moreover, eQTL are found disproportionately on SNP‐dense chromosome arms in C. elegans (Rockman, Skrovanek, & Kruglyak, ).…”

Tightly linked antagonistic-effect loci underlie polygenic phenotypic variation inC. elegans

“…If epistasis is systematically suppressive Hansen 2013), then the effects of isolated variants will routinely exceed their effects in their native genetic background. Such a pattern has been observed repeatedly in laboratory mice (Shao et al 2008;Tyler et al 2016), and several experiments have pointed to large stores of normally cryptic epistatic variation in C. elegans that can be exposed by genetic perturbations (Paaby et al 2015;Snoek et al 2017;Sterken et al 2017). Whether by repulsion-phase additive effects or tightly linked epistatic variants, C. elegans harbors a store of variation beyond that exposed by ordinary segregation.…”