The Evolution and Adaptive Potential of Transcriptional Variation in Sticklebacks—Signatures of Selection and Widespread Heritability

Abstract

Evidence implicating differential gene expression as a significant driver of evolutionary novelty continues to accumulate, but our understanding of the underlying sources of variation in expression, both environmental and genetic, is wanting. Heritability in particular may be underestimated when inferred from genetic mapping studies, the predominant “genetical genomics” approach to the study of expression variation. Such uncertainty represents a fundamental limitation to testing for adaptive evolution at the transcriptomic level. By studying the inheritance of expression levels in 10,495 genes (10,527 splice variants) in a threespine stickleback pedigree consisting of 563 individuals, half of which were subjected to a thermal treatment, we show that 74–98% of transcripts exhibit significant additive genetic variance. Dominance variance is also prevalent (41–99% of transcripts), and genetic sources of variation seem to play a more significant role in expression variance in the liver than a key environmental variable, temperature. Among-population comparisons suggest that the majority of differential expression in the liver is likely due to neutral divergence; however, we also show that signatures of directional selection may be more prevalent than those of stabilizing selection. This predominantly aligns with the neutral model of evolution for gene expression but also suggests that natural selection may still act on transcriptional variation in the wild. As genetic variation both within- and among-populations ultimately defines adaptive potential, these results indicate that broad adaptive potential may be found within the transcriptome.

Regulatory architecture of gene expression variation in the threespine stickleback, Gasterosteus aculeatus

“…of significant eQTL was 10.2 cM (range 1-86 cM), $1.77 Mb (range 0.03-22.19 Mb). Overall, trans-regulated expression traits did not exhibit more dominance variance than cis-regulated loci (transregulated loci, mean h 2 = 0.31, mean d 2 = 0.16; cis-regulated loci: mean h 2 = 0.37, mean d 2 = 0.18; values from Leder et al 2015).…”

“…Families were reared in separate 10 L tanks with density standardized to 15 individuals per tank, temperature at 17 6 1°, and 12:12 hr light/dark photoperiod. At the age of 6 months, 10 offspring from each family (five treated and five controls) were subjected to a temperature treatment as part of a related experiment (control: constant 17°; treatment: water gradually heated from 17 to 23°over 6 hr, see Leder et al 2015), and immediately killed for DNA and RNA collection.…”

“…RNA preparation, microarray design, and data normalization RNA preparation, gene expression microarrays, hybridization, and normalization procedures are described in detail in Leder et al (2009Leder et al ( , 2015. Briefly, total RNA was isolated from offspring liver tissue using standard protocols.…”

“…Genes with plastic vs. nonplastic expression To investigate whether genes exhibiting an alteration in expression level in response to a temperature stress treatment (i.e., those exhibiting environmental plasticity) had a different underlying regulatory architecture to those not exhibiting such a response, we divided genes into a "responding" and "nonresponding" group based on the results provided in the Supplementary Data for Leder et al (2015) and compared the frequency and position of cis-and trans-eQTL between the two groups.…”

“…Genes with plastic vs. nonplastic expression Following FDR correction, 4253 genes were found by Leder et al (2015) to exhibit a significant change in expression in response to a temperature treatment. We identified significant eQTL underlying 1131 of these genes (Table S4; eQTL type: 79.8% cis, 12.7% trans, 2.6% both, and 4.9% unknown).…”