The purpose of this book is to present a new theory of mutation-driven evolution, which is based on recent advances in genomics and evolutionary developmental biology. This theory asserts that the driving force of evolution is mutation and natural selection is of secondary importance.

What does it mean to say that mutation is random? How does mutation influence evolution? Are mutations merely the raw material for selection to shape adaptations? The author draws on a detailed knowledge of mutational mechanisms to argue that the randomness doctrine is best understood, not as a fact-based conclusion, but as the premise of a neo-Darwinian research program focused on selection. The successes of this research program created a blind spot - in mathematical models and verbal theories of causation - that has stymied efforts to re-think the role of variation. However, recent theoretical and empirical work shows that mutational biases can and do influence the course of evolution, including adaptive evolution, through a first come, first served mechanism. This thought-provoking book cuts through the conceptual tangle at the intersection of mutation, randomness, and evolution, offering a fresh, far-reaching, and testable view of the role of variation as a dispositional evolutionary factor. The arguments will be accessible to philosophers and historians with a serious interest in evolution, as well as to researchers and advanced students of evolution focused on molecules, microbes, evo-devo, and population genetics.

A thought-provoking exploration of deleterious mutations in the human genome and their effects on human health and wellbeing Despite all of the elaborate mechanisms that a cell employs to handle its DNA with the utmost care, a newborn human carries about 100 new mutations, originated in their parents, about 10 of which are deleterious. A mutation replacing just one of the more than three billion nucleotides in the human genome may lead to synthesis of a dysfunctional protein, and this can be inconsistent with life or cause a tragic disease. Several percent of even young people suffer from diseases that are caused, exclusively or primarily, by pre ]existing and new mutations in their genomes, including both a wide variety of genetically simple Mendelian diseases and diverse complex diseases such as birth anomalies, diabetes, and schizophrenia. Milder, but still substantial, negative effects of mutations are even more pervasive. As of now, we possess no means of reducing the rate at which mutations appear spontaneously. However, the recent flood of genomic data made possible by next-generation methods of DNA sequencing, enabled scientists to explore the impacts of deleterious mutations on humans with previously unattainable precision and begin to develop approaches to managing them. Written by a leading researcher in the field of evolutionary genetics, Crumbling Genome reviews the current state of knowledge about deleterious mutations and their effects on humans for those in the biological sciences and medicine, as well as for readers with only a general scientific literacy and an interest in human genetics. Provides an extensive introduction to the fundamentals of evolutionary genetics with an emphasis on mutation and selection Discusses the effects of pre-existing and new mutations on human genotypes and phenotypes Provides a comprehensive review of the current state of knowledge in the field and considers crucial unsolved problems Explores key ethical, scientific, and social issues likely to become relevant in the near future as the modification of human germline genotypes becomes technically feasible Crumbling Genome is must-reading for students and professionals in human genetics, genomics, bioinformatics, evolutionary biology, and biological anthropology. It is certain to have great appeal among all those with an interest in the links between genetics and evolution and how they are likely to influence the future of human health, medicine, and society.

The Arthur M. Sackler Colloquia of the National Academy of Sciences address scientific topics of broad and current interest, cutting across the boundaries of traditional disciplines. Each year, four or five such colloquia are scheduled, typically two days in length and international in scope. Colloquia are organized by a member of the Academy, often with the assistance of an organizing committee, and feature presentations by leading scientists in the field and discussions with a hundred or more researchers with an interest in the topic. Colloquia presentations are recorded and posted on the National Academy of Sciences Sackler colloquia website and published on CD-ROM. These Colloquia are made possible by a generous gift from Mrs. Jill Sackler, in memory of her husband, Arthur M. Sackler.

This text is about the central role of evolution in shaping the nature and diversity of the living world. It describes the processes of natural selection, how adaptations arise, and how new species form, as well as summarizing the evidence for evolution

The idea of mutation has changed considerably from the pre-Mendelian concepts of Darwin's generation to today's up-to-the-minute genomic context of mutation. The historical approach taken by History of Mutation reveals the way science works, incrementally by small steps rather than by dramatic, and rare, paradigm shifts.

The availability of genomic blueprints for hundreds of species has led to a transformation in biology, encouraging the proliferation of adaptive arguments for the evolution of genomic features. This text explains why the details matter and presents a framework for how the architectural diversity of eukaryotic genomes and genes came to arise.

This book, written by Motoo Kimura (1924–94), is a classic in evolutionary biology. In 1968, Kimura proposed the “neutral theory of molecular evolution”, which became the theoretical basis of modern evolutionary studies. After publishing his work in 1983 in the book “Neutral Theory of Molecular Evolution”, Kimura wrote this book in 1988 for the general public. It was originally written in Japanese and is translated here for the first time. In the book, Kimura first summarizes the development of evolutionary theory since Lamarck and Darwin. He then shows how the search for mechanisms of evolution developed into population genetics and describes how the study of molecular evolution matured by taking in the fruits of molecular biology. Kimura proceeds to carefully explain his neutral evolution theory at the molecular level. Finally, he presents his view of the world from an evolutionary perspective. The book has long served as an in-depth introduction to evolutionary biology for students and young researchers in Japan. There has been remarkably rapid progress in the field of bioscience at the molecular level over the past 30 years. Nevertheless, the book remains an important contribution that laid the foundations for what followed in molecular evolutionary studies.

An enduring controversy in evolutionary biology is the genetic basis of adaptation. Darwin emphasized "many slight differences" as the ultimate source of variation to be acted upon by natural selection. In the early 1900’s, this view was opposed by "Mendelian geneticists", who emphasized the importance of "macromutations" in evolution. The Modern Synthesis resolved this controversy, concluding that mutations in genes of very small effect were responsible for adaptive evolution. A decade ago, Allen Orr and Jerry Coyne reexamined the evidence for this neo-Darwinian view and found that both the theoretical and empirical basis for it were weak. Orr and Coyne encouraged evolutionary biologists to reexamine this neglected question: what is the genetic basis of adaptive evolution? In this volume, a new generation of biologists have taken up this challenge. Using advances in both molecular genetic and statistical techniques, evolutionary geneticists have made considerable progress in this emerging field. In this volume, a diversity of examples from plant and animal studies provides valuable information for those interested in the genetics and evolution of complex traits.

It is said that "necessity is the mother of invention". To be sure, wheels and pulleys were invented out of necessity by the tenacious minds of upright citi zens. Looking at the history of mankind, however, one has to add that "Ieisure is the mother of cultural improvement". Man's creative genius flourished only when his mind, freed from the worry of daily toils, was permitted to entertain apparently useless thoughts. In the same manner, one might say with regard to evolution that "natural selection mere(y tnodifted, while redundanry created". Natural selection has been extremely effective in policing alleHe mutations which arise in already existing gene loci. Because of natural selection, organisms have been able to adapt to changing environments, and by adaptive radiation many new species were created from a common ancestral form. Y et, being an effective policeman, natural selection is extremely conservative by nature. Had evolution been entirely dependent upon natural selection, from a bacterium only numerous forms of bacteria would have emerged. The creation of metazoans, vertebrates and finally mammals from unicellular organisms would have been quite impos sible, for such big leaps in evolution required the creation of new gene loci with previously nonexistent functions. Only the cistron which became redun dant was able to escape from the relentless pressure of natural selection, and by escaping, it accumulated formerly forbidden mutations to emerge as a new gene locus.