Microenvironmental Gene Expression Plasticity Among IndividualDrosophila melanogaster

Abstract

Differences in phenotype among genetically identical individuals exposed to the same environmental condition are often noted in genetic studies. Despite this commonplace observation, little is known about the causes of this variability, which has been termed microenvironmental plasticity. One possibility is that stochastic or technical sources of variance produce these differences. A second possibility is that this variation has a genetic component. We have explored gene expression robustness in the transcriptomes of 730 individual Drosophila melanogaster of 16 fixed genotypes, nine of which are infected with Wolbachia. Three replicates of flies were grown, controlling for food, day/night cycles, humidity, temperature, sex, mating status, social exposure, and circadian timing of RNA extraction. Despite the use of inbred genotypes, and carefully controlled experimental conditions, thousands of genes were differentially expressed, revealing a unique and dynamic transcriptional signature for each individual fly. We found that 23% of the transcriptome was differentially expressed among individuals, and that the variability in gene expression among individuals is influenced by genotype. This transcriptional variation originated from specific gene pathways, suggesting a plastic response to the microenvironment; but there was also evidence of gene expression differences due to stochastic fluctuations. These observations reveal previously unappreciated genetic sources of variability in gene expression among individuals, which has implications for complex trait genetics and precision medicine.

Mean-Variance QTL Mapping on a Background of Variance Heterogeneity

“…Since the recognition that variance effects can be attributable to individual genes, a growing body of research has asked questions about the prevalence of such effects , their evolutionary origins (canalization, robustness), their ramifications (decanalization in disease, increased variation) (Gibson 2009;Freund et al 2013;Lin et al 2016), and how the identification of such genes can provide a signal of, and thereby serve as a route to identify, higher order interactions such as epistasis or GxE (Struchalin et al 2010;Rönnegård and Valdar 2012;Forsberg and Carlborg 2017). These studies have promoted detection of variance heterogeneity as path to new biological discovery.…”

“…Environmental sources of residual variance heterogeneity have been well-documented, and include, for example, soil nitrogen and irrigation (Makumburage and Stapleton 2011), temperature (Shen et al 2014), and even the age at which young birds begin to experience the environmental insults outside of the nest (Snell-Rood et al 2015). Genetic sources of residual variance heterogeneity have attracted increasing interest, with multiple studies finding instances of the residual variance being heritable (Sorensen and Waagepetersen 2003;Hill and Mulder 2010;Sorensen et al 2015;Gonzalez et al 2016;Lin et al 2016;Mitchell et al 2016), and in some cases substantially attributable to allelic variation in individual genes (Paré et al 2010;Wolc et al 2012;Yang et al 2012;Hulse and Cai 2013;Wang et al 2014;Ayroles et al 2015;Forsberg et al 2015;Ivarsdottir et al 2017).…”

Widespread inter‐individual gene expression variability in Arabidopsis thaliana

“…Noise in gene expression has been shown to have a significant impact on the design and function of genetic circuits in unicellular organisms (Elowitz et al, 2002;Eldar & Elowitz, 2010). It has also been observed in multiple pathways in mammalian cells (Yin et al, 2009;Mantsoki et al, 2016;Riddle et al, 2018), in Drosophila cells (Pare et al, 2009) and between individuals in Drosophila (Lin et al, 2016). However, gene expression variability has mostly been analysed for a few individual genes in plants at a single-cell resolution (Angel et al, 2015;Araujo et al, 2017;Meyer et al, 2017;Gould et al, 2018).…”

Differential gene expression inDrosophila melanogasterandD. nigrosparsainfected with the sameWolbachiastrain

“…With regard to the variation among pools of individuals within replicate lines, gene expression can be influenced by several factors such as the environment and individual variation (Wittkopp, 2007). For example, around 23 percent of the genes in D. melanogaster are expressed differently at the individual level, which could be due to individual variation in size or weight (Lin et al ., 2016). In our study, we cannot evaluate an impact of individual variation as we used a pool of five individual flies per replicate, but, in any case, we would perhaps have seen less variation among pools if we had pooled more than five individuals per replicate.…”