Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK.
J Physiol. 2024 Jun;602(11):2547-2563. doi: 10.1113/JP284420. Epub 2023 Nov 7.
'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.
“魏斯曼氏屏障”(Weismann's barrier)在很大程度上限制了遗传理论,使其只能研究基因组变异的传递。然而,随着 DNA 甲基化和组蛋白修饰等基因调控的表观遗传机制的发现和阐明,人们对获得性性状遗传的研究重新产生了兴趣,并为其提供了机制上的合理性。尽管现在很清楚,这些机制允许许多环境获得的性状传递给后代,但身体如何将表型信息传递给其配子仍然是一个谜。在这里,我们讨论了最近的证据,表明这种通讯是由体内 RNA 介导的,这些 RNA 在内含体小泡(extracellular vesicles)中移动到配子中,在那里它们重新编程后代的表观基因组和表型。配子如何了解身体的变化不仅对临床有影响,而且通过将表型可塑性和适应性的个体内和代际机制结合在一起,对进化理论也有影响。