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. 2017 Jun 29;18(1):500.
doi: 10.1186/s12864-017-3899-8.

Contribution of Trans Regulatory eQTL to Cryptic Genetic Variation in C. Elegans

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Free PMC article

Contribution of Trans Regulatory eQTL to Cryptic Genetic Variation in C. Elegans

Basten L Snoek et al. BMC Genomics. .
Free PMC article

Abstract

Background: Cryptic 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.

Results: We 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.

Conclusions: These 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.

Keywords: Caenorhabditis elegans; Cryptic genetic variation; Genetical genomics; Heat stress; Trans-band; eQTL; eQTL hotspot.

Conflict of interest statement

Ethics approval and consent to participate

Ethics approval and consent does not apply because this study is based on non-regulated invertebrates.

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The authors declare this not relevant.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Effect of treatment on gene expression. a The RIL populations were exposed to three treatments: control (48 h at 20 °C), heat stress (46 h at 20 °C and 2 h at 35 °C), and recovery (as heat stress, with an additional 2 h at 20 °C). At the end of these treatments, the nematodes were in the L4 stage, and were harvested. Thereafter RNA was isolated and the transcriptome was measured by microarray. b The outcome of the treatment analysis. On the left a legend is included to clarify which contrasts are compared. On the right, the overlap in differentially expressed genes is shown per treatment comparison. For example, 942 genes are uniquely differentially expressed in the recovery treatment, these genes are differently expressed between recovery and heat stress and between recovery and control, but not between heat stress and control
Fig. 2
Fig. 2
Identified eQTL in control (left), heat stress (middle), and recovery (right) treatments, with a threshold of -log10(p) > 3.9 (FDR ≤ 0.05) in each treatment. The eQTL peak position is shown on the x-axis and gene position is shown on the y-axis. The cis-eQTLs (within 1 Mb of the gene) are shown in black and the trans-eQTLs in blue (control), red (heat stress), or green (recovery). The horizontal bars indicate the confidence interval of the eQTL. The chromosomes are indicated on the top and right of the plot. The histogram under the plot shows the eQTL density per 0.5 Mb bin
Fig. 3
Fig. 3
Overlap in cis- and trans-eQTL between conditions. a The overlap in genes with a cis-eQTL between conditions. QTL were selected based on FDR ≤ 0.05 per condition, a QTL was scored as overlapping if the same gene had a cis-eQTL in another condition. b The overlap in genes with a trans-eQTL between conditions. QTL were selected based on FDR ≤ 0.05 per condition, a QTL was scored as overlapping if the same gene had a trans-eQTL in another condition. The location was not yet considered in this analysis (see Additional file 16A). c The three genes with a cis-eQTL displaying genotypic plasticity, where the direction of the effect switches between environments. For all three genes: C52E2.4, C54D10.9, and nhr-226 the plastic response is apparent between the heat stress and recovery treatment
Fig. 4
Fig. 4
Genes with treatment specific trans-eQTL. a The expression patterns over the three treatments are shown for flp-22, pqm-1, and sod-5, the location mentioned is the location of the gene. The x-axis is organized per treatment (ct, control; hs, heat stress; rec, recovery). On the y-axis the log2 normalized expression is shown (b) The eQTL patterns for the same three genes. The x-axis shows the position along the chromosomes and the y-axis the significance of the association. The horizontal dashed line indicates the FDR ≤ 0.05 (−log10(p) > 3.9). Colors indicate the three treatments
Fig. 5
Fig. 5
The trans-eQTL of gei-7. a The eQTL patterns for gei-7, the x-axis shows the position along the chromosomes and the y-axis the significance of the association. The horizontal dashed line indicates the FDR ≤ 0.05 (−log10(p) > 3.9). Colors indicate the three treatments (control, blue; heat stress, red; recovery, green). b The genotype effects split out at the minor heat stress QTL (chromosome IV). c The genotype effects split out at the major QTL (chromosome V)
Fig. 6
Fig. 6
Genes belonging to the dopaminergic neuron anatomy term with a trans-eQTL. The trans-eQTL position of the genes is shown (n = 133 in control, n = 281 in heat stress, and n = 91 in recovery)

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