NR AWAI
AU Mary,C.P.J.
TI Molecular mechanism based on self-replicating protein conformation for the inheritance of acquired information in humans
QU Medical Hypotheses 2006; 67(5): 1164-9
PT journal article
AB Recent evidence challenges the paradigmatic view of nucleic acids as the sole mediators of hereditary information. Here I present a molecular mechanism that can explain how acquired information in humans in a DNA independent mode becomes innate and heritable. The model is based on self-replicating protein conformations, a concept derived from prion and amyloid biology. Information is stored in specific ß-sheet protein conformations that can act as cytoplasmic molecular memories. The conformational information can be transmitted to next generations in a non-nucleic acid based inheritance system utilizing the self-perpetuating potential of such ß-rich protein aggregates. Chaperones play a crucial role in the model by regulating and balancing the process of folding and misfolding; they also assist in preventing the development of aggregation-based disease. The protein conformation-mediated information system could represent an evolutionary conserved primordial mechanism: while the main strategy has been to ensure rapid folding of polypeptides into the native, functional conformation, the disfolded, ß-rich amyloidogenic state has provided advantage by providing a cytoplasmic, protease-resistant self-perpetuating DNA-independent adaptive inheritance system. The model offers an explanation for the problematic question of the evolution of complex behavioural traits and has even impact in the context of mammalian cloning: the protein conformation-based information localized in the somatic cytoplasm is lost when transferring nuclei only into enucleated oocytes. The protein conformation-based model presented herein postulates that proteins may contain much more information than determined by the nucleotide-triplet controlled peptide sequence and that there exists cross-talk and information exchange between proteins.
SP englisch