The Evolution Of Stress Induced Mutagenesis

The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.

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Concern is often expressed that our environment may include an increasingly large variety of mutagens, but the extent of the potential hazard they pose has yet to be fully evaluated. A variety of empirical procedures has been devised with which to estimate the mutagenic potency of suspect agents, and the relative merits of different tests are currently under debate. Although such tests are of great value, and are indeed indispensable, they are not, nevertheless, sufficient. In the long term, accurate estimation of hazard will also require a better understanding of the various mechanisms of mutagenesis, and in many instances these remain remarkably elusive. Our knowledge and appreciation of the problem has increased substantially over the last few years, but the precise way in which many mutagens cause mutations is not yet known. The aims of this conference were therefore two-fold. The first was to survey present information about mutagenic mechanisms, drawing together data from work with various experimental approaches and organisms, in order to discern the principles governing the action of different mutagens. The second was to examine the implications of such principles for the execution and evaluation of test procedures, and critically assess the research areas that need further attention in order to improve the interpretation of test results. Chris Lawrence v ACKNOWLEDGEMENT We gratefully acknowledge the support provided for this Conference by the U.,S. Department of Energy, The Foundation for Microbiology, Exxon Corporation and the University of Rochester.

Concerted efforts to study starvation and survival of nondifferentiating vegeta tive heterotrophic bacteria have been made with various degrees of intensity, in different bacteria and contexts, over more than the last 30 years. As with bacterial growth in natural ecosystem conditions, these research efforts have been intermittent, with rather long periods of limited or no production in between. While several important and well-received reviews and proceedings on the topic of this monograph have been published during the last three to four decades, the last few years have seen a marked increase in reviews on starvation survival in non-spore-forming bacteria. This increase reflects a realization that the biology of bacteria in natural conditions is generally not that of logarithmic growth and that we have very limited information on the physiology of the energy-and nutrient-limited phases of the life cyde of the bacterial cello The growing interest in nongrowing bacteria also sterns from the more recent advances on the molecular basis of the starvation-induced nongrowing bacterial cello The identification of starvation-specific gene and protein re sponders in Escherichia coli as weIl as other bacterial species has provided molecular handles for our attempts to decipher the "differentiation-like" responses and programs that nondifferentiating bacteria exhibit on nutrient limited growth arrest. Severallaboratories have contributed greatly to the progress made in life after-log research.

Gain new insight on utilizing bacterial stress responses to better combat bacterial infection with antibiotics and improve biotechnology. • Reviews the vast number of new findings that have greatly advanced the understanding of bacterial stress responses in the past 10 years. • Explores general regulatory principles, including the latest findings from genomics studies, including new research findings on both specific and general stress responses. • Details how stress responses affect the interactions between bacteria and host cells and covers bacterial stress responses in different niches and communities, with an emphasis on extreme environments.

Ionizing radiation mytagenesis. Chemical mutagenesis. Frameshift mutagenesis. Misrepair mutagenesis. The genetic determination and evolution of mutation rates.

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.