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In this paper, we demonstrate (1) how harnessing stochasticity can be the basis of creative agency; (2) that such harnessing can resolve the apparent conflict between reductionist (micro-level) accounts of behaviour and behaviour as the outcome of rational and value-driven (macro-level) decisions; (3) how neurophysiological processes can instantiate such behaviour; (4) The processes involved depend on three features of living organisms: (a) they are necessarily open systems; (b) micro-level systems therefore nest within higher-level systems; (c) causal interactions must occur across all the boundaries between the levels of organization. The higher levels constrain the dynamics of lower levels. The experimental evidence and theoretical arguments are shown to be consistent with previous research on the neuronal mechanisms of conscious choice, and with the interconnected multi-level processes by which organisms harness stochasticity, whether conscious or unconscious., Author(s): Raymond Noble [sup.1], Denis Noble [sup.2] Author Affiliations: (1) grid.83440.3b, 0000000121901201, Institute for Women's Health, University College London, , WC1E 6AU, London, UK (2) grid.4991.5, 0000 0004 1936 8948, [...]

A chance mutation affecting a single or extremely few individuals in a continuous population will be quickly diluted through interbreeding. Charles Darwin fully appreciated this difficulty with relying on natural selection alone, and suggested an enabling role for geographical isolation in the origin of species. However, Darwin also believed in evolution by the inheritance of acquired traits and in populations of interbreeding animals, both of which would need a different isolating mechanism to overcome dilution and play a role in animal evolution. Historically disputed, the inheritance of acquired characters is now increasingly accepted as a phenomenon, and Charles Darwin himself is acknowledged as closely pre‐empting the type of physiology necessary to mediate it in his hypothesis of 'pangenesis'. In this article, we question how the inheritance of acquired traits might overcome the problem of dilution by interbreeding and contribute to evolution. Specifically, we describe how Darwin's young protégé, George Romanes, developed ideas he discussed with Darwin and extended pangenesis to include a conceivable solution published after Darwin's death: physiological selection of fertility. In light of the 'rediscovery' of pangenesis, here we recount physiological selection as a testable hypothesis to explain how environmentally acquired characteristics could become coupled to the generation of species. [ABSTRACT FROM AUTHOR]

'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. [ABSTRACT FROM AUTHOR]