Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine, Second Edition transports readers from Mendelian genetics to 4D genomics, building a case for genes and genomes as distinct biological entities, and positing that the genome, rather than individual genes, defines system inheritance and represents a clear unit of selection for macroevolution. In authoring this thought-provoking text, Dr. Henry Heng invigorates fresh discussions in Genome Architecture Theory and helps readers reevaluate their current understanding of human genetics, evolution, and new pathways for advancing molecular and precision medicine. In this fully updated, new edition Dr. Heng fully embraces the integration of system information with genome-mediated evolutionary mechanisms, and supports this framework with recent findings and growing, interdisciplinary research supporting Genome Architecture Theory. Ten evidence-based chapters discuss 4D genomics, genes, and genomes as distinct biological entities, genome chaos and macrocellular evolution, karyotype coding and fuzzy inheritance, as well as an entirely novel information flow-driven model of evolution, and more. All new chapters consider the creation and maintenance of system information for complexity and biodiversity, as well as modes of analyzing information-based and historically contingent evolutionary theory. This synthesis offers an updated evolutionary theory, unifying physical, chemical, and biological mechanisms within organismal systems, and details the evolution of information packages where information flow, matter arrangement, and energy interact.