No abstract

Intergenerational inheritance of transcriptional responses induced by low temperature rearing has recently been shown in Drosophila. Besides germline inheritance, fecal transfer experiments indirectly suggested that the acquired microbiome may also have contributed to the transcriptional responses in offspring. Here, we analyze expression data on inheritance of the cold‐induced effects in conjunction with previously reported transcriptomic differences between flies with a microbiota or axenic flies and provide support for a contribution of the acquired microbiome to the offspring phenotype. Also, based on a similar analysis in conjunction with diet‐ and metabolism‐related fly transcriptome data, we predicted and, then, experimentally confirmed that cold regulates triglyceride levels both inter‐ as well as trans‐generationally.

Evidence supporting non-DNA sequence-based inheritance in animals has increasingly been described, often under short-term, intergenerational inheritance or longer, transgenerational epigenetic inheritance (TEI). Mammalian evidence for the latter, a stronger indicator of germline transmission, is however considered controversial due to inherent confounders. Overall, evolutionary and physiological implications of non-genetic inheritance mostly remain speculative. Here, in an innovative, unbiased, and all-inclusive approach, we examined existing transcriptomic data associated with so far available Drosophila models of inter- and trans-, and rodent models of inter-generational inheritance, uncovered model-matching interchangeable responses between species, and found phenotypic directionality switching in transgenerational flies. We then predicted a physiological metabolic trigger modeled in mice, not Drosophila, to induce in the latter TEI similarly showing interchangeable responses and phenotypic directionality switching. We finally confirmed these predictions experimentally in flies. The observed phenotypic cross-species portability and cross-generational directionality shift support evolutionary conservation, and adaptive and maladaptive significance of non-genetic inheritance.

Non-DNA sequence-based inheritance of phenotypic traits across organismal generations, with factors like DNA methylation, histone modifications and RNAs, as also chromatin states, potentially carrying the heritable information, is a subject of immense cur-