Genomes, Proteomes, and the Central Dogma
Sarah Franklin, PhD and Thomas M. Vondriska, PhD
- Author Affiliations
From the Departments of Anesthesiology (S.F., T.M.V.), Medicine (T.M.V.) and Physiology (T.M.V.), David Geffen School of Medicine, University of California, Los Angeles, CA.
Correspondence to Sarah Franklin or Thomas M. Vondriska, Departments of Anesthesiology, Medicine & Physiology, David Geffen School of Medicine, BH 557 CHS Bldg, 650 Charles Young Dr, Los Angeles, CA 90095. E-mail firstname.lastname@example.org or email@example.com
Key Words: genomics heart failure proteomics
Arguably the greatest postmodern coup for reductionism in biology was the articulation of the central dogma. 1 Not since “humors” were discarded from medical practice and logic and experiment instituted as the cornerstones of physiology (which they remain today) had such a revolutionary idea transformed biology and enabled scientific inquiry. Because of its simplicity, the central dogma has the tantalizing allure of deduction: If one accepts the premises (that DNA encodes mRNA, and mRNA, protein), it seems one cannot deny the conclusions (that genes are the blueprint for life). As a result, the central dogma has guided research into causes of disease and phenotype, as well as constituted the basis for the tools used in the laboratory to interrogate these causes for the past half century.
The past decade, however, has witnessed a rapid accumulation of evidence that challenges the linear logic of the central dogma. Four previously unassailable beliefs about the genome—that it is static throughout the life of the organism; that it is invariant between cell type and individual 2–4; that changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution 5); and that necessary and sufficient information for cellular function is contained in the gene sequence—have all been called into question in the last few years. Revelations of similar scale have occurred in the transcriptome, with the discovery of the ubiquity (and variety) of mRNA splicing. 6 So too with the proteome, which has undergone perhaps the most dramatic shift in …