An organism's phenotype is the product of its environment and genotype, but an ancestor’s environment can also be a contributing factor. The recent increase in caloric intake and decrease in physical activity of developed nations' populations is contributing to deteriorating health and making the study of the longer term impacts of a changing lifestyle a priority. The dietary habits of ancestors have been shown to affect phenotype in several organisms, including humans, mice, and the fruit fly. Whether the ancestral dietary effect is purely environmental or if there is a genetic interaction with the environment passed down for multiple generations, has not been determined previously. Here we used the fruit fly, Drosophila melanogaster, to investigate the genetic, sex-specific, and environmental effects of a high fat diet for three generations’ on pupal body weights across ten genotypes. We also tested for genotype-specific transgenerational effects on metabolic pools and egg size across three genotypes. We showed that there were substantial differences in transgenerational responses to ancestral diet between genotypes and sexes through both first and second descendant generations. Additionally, there were differences in phenotypes between maternally and paternally inherited dietary effects. We also found a treated organism’s reaction to a high fat diet was not a consistent predictor of its untreated descendants’ phenotype. The implication of these results is that, given our interest in understanding and preventing metabolic diseases like obesity, we need to consider the contribution of ancestral environmental experiences. However, we need to be cautious when drawing population-level generalization from small studies because transgenerational effects are likely to exhibit substantial sex and genotype specificity.

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