Bubbling beyond the barrier: exosomal RNA as a vehicle for soma-germline communication

'Weismann's barrier' has restricted theories of heredity to the transmission of genomic variation for the better part of a century. However, the discovery and elucidation of epigenetic mechanisms of gene regulation such as DNA methylation and histone modifications has renewed interest in studies on the inheritance of acquired traits and given them mechanistic plausibility. Although it is now clear that these mechanisms allow many environmentally acquired traits to be transmitted to the offspring, how phenotypic information is communicated from the body to its gametes has remained a mystery. Here, we discuss recent evidence that such communication is mediated by somatic RNAs that travel inside extracellular vesicles to the gametes where they reprogram the offspring epigenome and phenotype. How gametes learn about bodily changes has implications not only for the clinic, but also for evolutionary theory by bringing together intra- and intergenerational mechanisms of phenotypic plasticity and adaptation.image Abstract figure legend The emerging soma-germline communications system mediating parental effects in numerous animal models projected onto humans. This new inheritance system relies on the transcription of RNAs in somatic tissues in response to various environmental factors that subsequently travel to the gametes inside extracellular vesicles. In parental gametes or the embryo, or both, these somatic RNAs reprogram the offspring phenotype through currently unknown (but broadly epigenetic) mechanism(s). This is contrasted with contemporary genetic inheritance mediated by recombination of germline DNA.image