A ‘phenotypic hangover’: the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster

Abstract

The Developmental Origins of Health and Disease hypothesis predicts that early-life environmental exposures can be detrimental to later-life health and that mismatch between the pre- and post-natal environment may contribute to the growing non-communicable disease epidemic. Within this is an increasingly recognized role for epigenetic mechanisms; for example, epigenetic modifications can be influenced by nutrition and can alter gene expression in mothers and offspring. Currently, there are few whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in Drosophila melanogaster. We manipulated Drosophila food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet and analysed the transcriptome of the F0–F3 generations by RNA sequencing. At F0, the altered (high-protein, low-carbohydrate) diet increased expression of genes classified as having roles in epigenetic processes, with co-ordinated down-regulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally induced gene expression changes demonstrate that dietary alterations can up-regulate epigenetic genes, which may influence the expression of genes with broad biological functions. Furthermore, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response to maternal nutrition, aiding the understanding of the interaction between maternal diet and offspring health, with direct implications for the current non-communicable disease epidemic.

Transgenerational inheritance of cold temperature response in Drosophila

“…Gene expression data related to various studies were used for gene overlap analysis, as outlined in Fig. A.…”

“…, it is essentially intergenerational, not transgenerational, as claimed, since only the first unexposed generation has been investigated. Given the profound current interest in transgenerational epigenetic inheritance , demonstration of which requires phenotypic analysis of at least a second unexposed generation , it will be compelling to examine if cold‐induced effects in flies extend beyond the first unexposed generation. Notably, intergenerational inheritance of cold‐induced effects has also been recently shown in mice .…”

“…As cold acclimation is associated with transcriptomic and metabolomic reorganization in D. melanogaster , we performed another gene overlap analysis to identify a candidate metabolic trait that might be inherited. In this analysis, differential genes related to cold treatment were compared with that related to feeding of high‐sugar , high‐fat , and high‐protein diets, and to functional studies of the metabolic genes Hnf4 , Sirt1 , Atf3 , and Hr96 . Together, triglyceride (TAG) level was identified as a promising candidate for phenotypic analysis in transgenerational experiments.…”

The influence of developmental diet on reproduction and metabolism in Drosophila

“…Altogether, the composition of the developmental diet has far-reaching consequences for Drosophila fitness. Nevertheless, there are only a few experimental studies in fruit flies [22,23], which had tested the adaptive significance of phenotypic changes caused by the developmental diet in the context of adult nutritional environments. It is therefore still an open question, whether such changes represent adaptive responses to the given developmental diet, as suggested, for example, by the PAR hypothesis, or rather are inevitable consequences of development under sub-optimal conditions.…”

Drosophila melanogaster as an alternative model organism in nutrigenomics

“…Studying diet-related effects on epigenetic mechanisms in fruit flies has just recently started [64,65]. The administration of diets with a varying macronutrient composition shows persistent changes of genes associated with epigenetic mechanisms over generations [64]. A study by Lian and co-workers [65] looked into the DNA methylation pattern of flies reared under dietary restriction.…”