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

J Physiol. 2024 Jun;602(11):2547-2563. doi: 10.1113/JP284420. Epub 2023 Nov 7.

Abstract

'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.

Keywords: Charles Darwin; epigenetics; extracellular RNA; extracellular vesicles; non‐Mendelian inheritance; pangenesis; reproductive physiology.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Communication
  • Epigenesis, Genetic
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Germ Cells* / physiology
  • Humans
  • RNA* / genetics

Substances

  • RNA