Self-Perpetuating Structural States in Biology, Disease, and Genetics

Book excerpt: Over the past half-century, the central dogma, in which DNA makes RNA makes protein, has dominated thinking in biology, with continuing refinements in understanding of DNA inheritance, gene expression, and macromolecular interactions. However, we have also witnessed the elucidation of epigenetic phenomena that violate conventional notions of inheritance. Protein-only inheritance involves the transmission of phenotypes by self-perpetuating changes in protein conformation. Proteins that constitute chromatin can also transmit heritable information, for example, via posttranslational modifications of histones. Both the transmission of phenotypes via the formation of protein conformations and the inheritance of chromatin states involve self-perpetuating assemblies of proteins, and there is evidence for some common structural features and conceptual frameworks between them. To foster interactions between researchers in these two fields, the National Academy of Sciences convened an Arthur M.Sackler Colloquium entitled "Self-Perpetuating Structural States in Biology, Disease, and Genetics" in Washington, DC, on March 22-24, 2002. Participants described new phenomenology and provided insights into fundamental mechanisms of protein and chromatin inheritance. Perhaps most surprising to attendees was emerging evidence that these unconventional modes of inheritance may be common.