|Year : 2020 | Volume
| Issue : 1 | Page : 25-27
Genome chaos: Redefying genetics, evolution, and environmental factors in medicine
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
|Date of Submission||22-Mar-2020|
|Date of Decision||24-Mar-2020|
|Date of Acceptance||24-Mar-2020|
|Date of Web Publication||21-Apr-2020|
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Zhang K. Genome chaos: Redefying genetics, evolution, and environmental factors in medicine. Environ Dis 2020;5:25-7
Book Title: Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine
Authors: Henry H. Heng
Paperback ISBN: 9780128136355
eBook ISBN: 9780128136362
Publisher: Academic Press
Published Date: May 29, 2019
Dr. Henry H. Heng recently published his genome theory in a book “Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine,” and it is now a PROSE award finalist. With eight chapters and 556 pages, this book covers an array of exciting yet challenging current issues: from large-scale genomics to evolutionary theory, cancer to other common and complex diseases, and basic research to molecular medicine. Unlike most books on these subjects, Genome Chaos critically evaluates well-accepted genomic/evolutionary concepts in the context of the newly discovered and long-ignored biological facts. By comparing gene-centric and genome-based perspectives, this book aims to initiate the much-needed conversation about the multiple levels of bio-inheritance, the dynamic pattern of cellular and organismal evolution, and the promises and limitations of molecular biology and precision medicine.
This book elegantly synthesizes the genome-based frameworks Dr. Heng developed over the last two decades. Based on the storyline of Dr. Heng's own journey searching for genome theory, this book can be divided into five episodes.
The first episode includes Chapters 1 (from Mendelian Genetics to 4D Genomics) and 2 (Genes and Genomes Represent Different Biological Entities). It defines the gene and genome both from historical and sequencing-era perspectives. Following a brief review of the transition from genetics to genomics in the context of the Human Genome Project, the current status and future direction of large-scale genomics are discussed. For example, the power of the gene is drastically reduced, whereas gaps between genotype and phenotype increase. Ultimately, it is realized that genome-level system operation is not simply a matter of “adding up” the function of individual parts (genes), and any gene is defined by its genomic context. Hence, a new genome-based genomic paradigm is in order.
The second episode includes Chapters 3 (Genome Chaos and Macrocellular Evolution: How Evolutionary Cytogenetics Unravels the Mystery of Cancer) and 4 (Chromosomal Coding and Fuzzy Inheritance: The Genomic Basis of Bio-information and Heterogeneity). This part summarizes over two decades' worth of experimental and theoretical discoveries in Dr. Heng's laboratory. Following a brief introduction of the historical concepts of cancer research and main discoveries of Cancer Genome Project, the cancer gene mutation theory and many other alternative cancer theories are critically evaluated. As cancer represents a typical adaptive system, watching karyotype evolution in action, experiments are performed to illustrate the pattern of somatic evolution during cellular immortalization. This experiment leads to the discovery of two-phased cancer evolution (macro- and microcellular evolution separated by genome instability), genome chaos (rapid and massive genome re-organization), and a genome-based cancer evolutionary model. Together, these analyses downplay the importance of cancer gene mutation-mediated individual molecular mechanisms. In contrast, it is shown that diverse molecular mechanisms of cancer can be unified by an evolutionary mechanism including stress, cellular adaptation and trade-offs, new emergent genomes, and cancer gene-mediated population growth. This new model, supported by cancer genome sequencing data, challenges the key assumptions it set out to prove: the gene mutation theory of cancer. Dr. Heng calls for new platforms for both cancer diagnosis and treatment. Furthermore, to explain why chromosomes are so important in cancer evolution, and the mechanism for cellular heterogeneity, the concepts of karyotype coding and fuzzy inheritance are introduced. These concepts are crucial building blocks for a new, logical framework of bio-inheritance.
The third episode, Chapters 5 (Why Sex: Genome Reinterpretation Dethrones the Queen) and 6 (Breaking the Genome Constraint: The Mechanism of Macroevolution), goes beyond cancer research. The genome theory is applied to organismal evolution in other noncancer systems. This episode addresses, and perhaps answers, two of the most challenging questions in evolutionary biology:
The question of “why sex” represents one of the biggest mysteries in biology. Although the last century has generated many hypotheses, a common thread among them assumes that sex increases genetic diversity through meiosis. Totally surprisingly, a genome-based lens suggests that the primary function of sex is to maintain the genome-defined system (the species) by preserving karyotype coding through meiotic pairing. A computer simulation study is performed to support this new revelation.
The question of “what is the mechanism for speciation” has puzzled most evolutionary scholars prior to Darwin's time. Even though natural selection explains microevolution well, how microevolution leads to macroevolution is still controversial. Specifically, it has been hard to demonstrate the key mechanistic assumption that an accumulation of microevolution over time leads to macroevolution. Based on experimental facts observed from somatic evolution and the aforementioned newly realized function of sex, the relationships between artificial and natural selection, gene dynamics and genome constraint, and micro- and macroevolution are compared. Such syntheses suggest that the macroevolution usually is not achieved by microevolution accumulation over time! A multiple-phase model of speciation is then proposed to replace natural selection. In this model, (a) the initial speciation is triggered by genome alterations that break down the boundary of parental genomes (the phase of creating new genome); (b) speciation is achieved by mating with partner(s) of similar altered genomes to produce fertile offspring (the phase of establishing new members of the population); and (c) the population grows over a long period of time (microevolutionary phase, possibly involving natural selection to form stable and long-lasting species). The new concept of how evolution works leads to the re-interpretation of many long-standing questions. Is the concept of species correct? Is speciation a rapid or slow process? Why does species (adaptive) radiation often followed by massive extinctions? Why is it challenging to identify genes responsible for speciation? Together, the key limitations of Darwin's natural selection in macroevolution are systematically, and importantly, illustrated.
The fourth episode, Chapter 7 (The Genome Theory: A New Framework), summarizes 12 principles of the genome theory. The key message is that the genome represents the highest level of genomic information; the genome functions not only as the carrier of genes but also as the organizer of gene/epigenetic interaction. Furthermore, genome re-organization represents an effective way to create new genomic information. Such species-specific information is essential both for somatic and organismal evolution. The genome theory reconciles somatic dynamics (for short-term adaptation) and germline constraint (for long-term existence) and unifies genomic and evolutionary theories.
The final episode is Chapter 8 (The Rationale and Challenges for Molecular Medicine). Following a brief historical review of molecular medicine, the rationales and challenges of precision medicine are presented. By applying the principles of the genome theory, the future direction of molecular medicine is discussed. Importantly, it is crucial to understand diseases in the context of adaptive systems and increased bio-uncertainty. This chapter also represents an example of how to apply the genome theory to rethink medicine.
This is an eye-opening book full of thought-provoking facts/ideas/syntheses. Despite a wide range of coverage, its rationales, organization of facts, and unique synthesis are exceptional. In addition to the new models both for somatic and organismal evolution, I am impressed by the concepts of system inheritance and fuzzy inheritance, which convincingly explain the dynamic relationship between the gene, genome, and environment. Because inheritance is by and large fuzzy, and environmental factors can select phenotypes within a genotype-defined potential range, the environmental contribution to many common and complex diseases will become increasingly important. This also explains why lifestyle change is often useful for the prevention and even treatment of common and complex diseases. With the acceptance of the limitations of genetic determinism, more research effort, including funding, should focus on environmental diseases.
This is a timely book that deserves more attention from multiple academic disciplines, and it belongs on reading lists for academic critical thinking in genetics/genomics, system biology, evolution, cancer research, molecular medicine, environmental disease, and scientific philosophy. Its collection of ignored facts, critical analysis of certain well-accepted concepts, and new way of synthesis on genomics and evolution have set a good example for us to follow. It is a must-read for the new generation of thinkers and researchers.
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Conflicts of interest
There are no conflicts of interest.