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 where the genome, rather than individual genes, defines system-level inheritance and represents a clear unit of selection for macroevolution. In 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 timely 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. Ten evidence-based chapters discuss 4D genomics, genes and genomes as distinct biological entities, genome chaos and cellular macroevolution, karyotype coding and fuzzy inheritance, as well as an entirely novel model of evolution driven by information flow, and more. Brand-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 framework. This synthesis offers a revolutionary paradigm of evolutionary theory. It also hypothesizes about how information flow, matter arrangement, and energy interact.