A unified vision of the building blocks of life

To the editor: From the discovery of DNA to the sequencing of the human genome, the template-dependent formation of biological molecules from gene to RNA and protein has been the central tenet of biology. Yet the origins of many diseases, including allergy, Alzheimer’s disease, asthma, autism, diabetes, inflammatory bowel disease, Lou Gehrig’s disease, multiple sclerosis, Parkinson’s disease and rheumatoid arthritis, continue to evade our understanding. Expectations that defined variation in the DNA blueprint would serve to pinpoint even multigenic causes of these diseases remain unfulfilled. Studies of distinct populations have implicated different genes, and those genes that are identified contribute to disease in a small fraction of the individuals diagnosed1–3. The genetic parts list seems insufficient to account for the origin of many grievous illnesses. Environmental factors including diet and microorganisms are also origins of disease. For example, type 2 diabetes, which affects hundreds of millions of people, is linked to a high-fat diet4, and this mechanism of disease onset is common to diverse species. When disease arises from a cellular response to a pathogen or environmental stimulus, genomics alone is unlikely to provide all the answers. This view is underscored by the observation that surprisingly similar numbers of genes exist in even the most divergent of life forms. Moreover, while the genome provides the framework and basic instruction upon which the cell develops and operates, the full complexity of cellular life cannot be directly encoded by it. As indivisible units of life, the cells of all organisms consist of four fundamental macromolecular components: nucleic acids (including DNA