The detection of DNA as the transforming principle in bacteria 95 years ago, almost immediately led to 1) refutation of the old and heavily disputed concept of inheritance of acquired featured, since this would necessitate rewriting of “the book of life” by environmental factors, such as nutrition, stress, and 2) exclusion of the existence of any matter of inheritance different from DNA and genes. In this opinion paper, it is intended to overcome this narrowing by the re-consideration of other cellular constituents, i.e., plasma membranes (PMs) and organelles as well as the previously identified extracellular vesicles (EVs) and micelle-like complexes, which may operate as vehicles of the transfer of so-called M(E)Ls from donor to acceptor cells, from parental to offspring organisms, as non-DNA matter of biological inheritance. M(E)Ls represent arrangements of integral and peripheral membrane proteins, glycosylphosphatidylinositol-anchored proteins (GPI-APs) and cytoskeletal protein components in concert with cholesterol and (glyco)phospholipids into structures of characteristic configuration and topology and function, e.g., blebs, protuberances, invaginations. Recent experimental studies have demonstrated that upon release from donor cells and subsequent transfer to and replication by mechanisms of self-organization (rather than self-assembly) in acceptor cells, those MELs induce novel metabolic phenotypes, such as stimulation of lipid and glycogen synthesis. Most crucial, in rats and humans the structure of MELs is susceptible to environmental factors, such as mechanical distortion, nutrition, which may contribute to phenotypic plasticity and the inheritance of acquired traits. Those epigenetic mechanisms, which are apparently not based on modifications of DNA and DNA-associated proteins, have not been adequately addressed so far in studies on the pathogenesis of common complex diseases. The presented opinion is aimed at the initial encouragement for the identification and characterization of some of the (most important) reasons for the adherence to the “DNA-/gene-centric” conception of biological inheritance for almost a century and the accompanying ongoing exclusion of intercellular and transgenerational transfer of non-DNA matter from the repertoire of (epi)genetic mechanisms for the explanation of phenotypic plasticity and the inheritance of acquired traits. The unraveling of the network of human and non-human actors constituting the apparatuses of the production and observation of the phenomenon of inheritance, including
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