Mapping determinants of gene expression plasticity by genetical genomics in C. elegans - PubMed (original) (raw)
. 2006 Dec 29;2(12):e222.
doi: 10.1371/journal.pgen.0020222. Epub 2006 Nov 13.
Olga Alda Alvarez, Evert W Gutteling, Marcel Tijsterman, Jingyuan Fu, Joost A G Riksen, Esther Hazendonk, Pjotr Prins, Ronald H A Plasterk, Ritsert C Jansen, Rainer Breitling, Jan E Kammenga
Affiliations
- PMID: 17196041
- PMCID: PMC1756913
- DOI: 10.1371/journal.pgen.0020222
Mapping determinants of gene expression plasticity by genetical genomics in C. elegans
Yang Li et al. PLoS Genet. 2006.
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 degrees C and 24 degrees 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 degrees 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.
Conflict of interest statement
Competing interests. The authors have declared that no competing interests exist.
Figures
Figure 1. Illustration of Temperature, eQTL, and pQTL (eQTL-by-Temperature Interaction) Effects
Genotype (N2 and CB4856) and temperature (16 °C and 24 °C) are two factors that might induce differential expression for transcripts. The colors of the animals correspond to the different gene expression levels. (A) Transcript with differential expression induced by temperature. The transcript is overexpressed at 24 °C independent of the genotype. (B) Transcript with strong eQTL effect. At both temperatures, worms with N2 genotype at a locus of interest show higher expression. (C) Transcript with pQTL effect. At 16 °C, transcripts show low expression in both genotypes. At 24 °C, only one allele (e.g., CB4856, as shown here) shows a strong induction of gene expression. If this upregulation is restricted to a specific tissue (the lower worm), it will be diluted in the total body when average of expression is measured (the upper worm). Other possible pQTL patterns can easily be conceived based on this example.
Figure 2. Venn Diagram Result of Joint Analysis
The figures indicate the number of transcripts detected with significant cis- and _trans_-eQTL or pQTL effect (p < 0.001 with FDR of 0.04 after multiple testing correction) in a full ANOVA model (see Materials and Methods for details). In the first Venn diagram, F.P refers to the number of estimated potential false positive eQTLs.
Figure 3. Volcano Plots for Temperature, eQTL, and pQTL Effect
The temperature (T) (A), eQTL (B), and pQTL (C) effects for all genes are plotted on the _x_-axes. (A) Temperature effect −log10 _p_-values from intensity-based analysis are plotted on the _y_-axis. (B and C) eQTL and pQTL −log10 _p_-values from full model are plotted on the _y_-axes. Vertical dashed lines correspond to 2-fold change in expression. The dotted lines indicate the significance thresholds: (A) FDR 0.01; (B) p = 0.001 for single and two-locus search; (C) p = 0.001 for genomewide (black), single-locus (green), and two-locus (blue) search.
Figure 4. Temperature-Dependent eQTL Effects
(A) Comparisons of eQTL and transcript positions for _trans_-regulated genes with significant eQTL and pQTL effects in the full model. The grey dotted horizontal lines separate the genome into different chromosomes. Grey and black circles indicate _trans_-regulated transcripts with significant eQTL effect and with significant pQTL effect, respectively, in the joint analysis. Among the transcripts with significant eQTL effect at both temperatures, a majority (72%) is _cis_-regulated (not included in the plot), while most of the transcripts (85%) with pQTL effect are _trans_-regulated. A horizontal transband was observed at 77.56 Mb (Chromosome V) by joint analysis. The transcripts falling into the region specified by dotted diagonals have _cis_-regulated eQTL (±2 Mb). (B) Comparison of eQTL effect for transcripts at two temperatures. (C) Comparison of temperature-induced differential expression (T effect) for transcripts at two genotypes. In (B) and (C), open and closed circles indicate _cis_-regulated and _trans_-regulated transcripts, respectively; grey and black circles are used for genes with significant eQTL and with significant pQTL effect, respectively. _Trans_-regulated transcripts in the 77.56Mb transband are colored blue.
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