Evolution of Virulence in Eukaryotic Microbes E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1426

Veröffentlichungsjahr: 2012

Beschreibung

A unique and timely review of the emergence of eukaryotic virulence in fungi, oomycetes, and protozoa, as they affect both animals and plants Evolution of Virulence in Eukaryotic Microbes addresses new developments in defining the molecular basis of virulence in eukaryotic pathogens. By examining how pathogenic determinants have evolved in concert with their hosts, often overcoming innate and adaptive immune mechanisms, the book takes a fresh look at the selective processes that have shaped their evolution. Introductory chapters ground the reader in principal evolutionary themes such as phylogenetics and genetic exchange, building a basis of knowledge for later chapters covering advances in genetic tools, how pathogens exchange genetic material in nature, and the common themes of evolutionary adaptation that lead to disease in different hosts. With the goal of linking the research findings of the many disparate scientific communities in the field, the book: * Assembles for the first time a collection of chapters on the diversity of eukaryotic microorganisms and the influence of evolutionary forces on the origins and emergence of their virulent attributes * Highlights examples from three important, divergent groups of eukaryotic microorganisms that cause disease in animals and plants: oomycetes, protozoan parasites, and fungi * Covers how the development of genetic tools has fostered the identification and functional analyses of virulence determinants * Addresses how pathogens exchange genetic material in nature via classical or modified meiotic processes, horizontal gene transfer, and sexual cycles including those that are cryptic or even unisexual * Provides a broad framework for formulating future studies by illustrating themes common to different pathogenic microbes Evolution of Virulence in Eukaryotic Microbes is an ideal book for microbiologists, evolutionary biologists and medical professionals, as well as graduate students, postdoctoral fellows, and faculty members working on the evolution of pathogens.

Leseprobe

Table of Contents

Cover

Title page

Copyright page

PREFACE

ACKNOWLEDGMENTS

CONTRIBUTORS

PART I: GENERAL OVERVIEWS

CHAPTER 1 POPULATION GENETICS AND PARASITE DIVERSITY

MUTATION

GENETIC DIVERSITY AND RANDOM GENETIC DRIFT

THE NEUTRAL THEORY

MUTATION AND SELECTION

EFFECTIVE POPULATION SIZE

VARIATION IN MUTATION RATES

WHAT CAN WE LEARN FROM POLYMORPHISM AND DIVERGENCE?

CONCLUSIONS

ACKNOWLEDGMENT

CHAPTER 2 EVOLUTION OF MEIOSIS, RECOMBINATION, AND SEXUAL REPRODUCTION IN EUKARYOTIC MICROBES

DEFINING SEX

MECHANISMS OF SEX

DETECTING SEXUAL REPRODUCTION

EVOLUTIONARY IMPACTS OF SEXUAL REPRODUCTION

ACKNOWLEDGMENTS

CHAPTER 3 PHYLOGENOMIC ANALYSIS

INTRODUCTION

ASSEMBLING DATA SETS FOR ANALYSES

MULTIPLE ALIGNMENT CONSTRUCTION AND EDITING

METHODS OF PHYLOGENETIC ESTIMATION

SELECTING AN APPROPRIATE PHYLOGENETIC MODEL

ASSESSING STATISTICAL SIGNIFICANCE

SYSTEMATIC ERROR AND DEALING PHYLOGENETIC ARTIFACTS

WHY PHYLOGENETIC SIGNALS OF DIFFERENT GENES CAN DIFFER AND WHY IT MATTERS

CONCLUSIONS

CHAPTER 4 PHYLOGENETICS AND EVOLUTION OF VIRULENCE IN THE KINGDOM FUNGI

GENERAL CONCEPTS ON FUNGAL EVOLUTION

FUNGAL PHYLOGENY

MECHANISMS TO GENERATE GENETIC DIVERSITY

EVOLUTION OF FUNGAL PATHOGENS

CONCLUDING REMARKS

PART II: POPULATION GENETICS AND EVOLUTIONARY APPROACHES

CHAPTER 5 MALARIA: HOST RANGE, DIVERSITY, AND SPECIATION

EARLY PHYLOGENETIC STUDIES

THE ORIGIN OF P. FALCIPARUM

THE ORIGIN OF P. VIVAX

P. OVALE AND P. MALARIAE

HOST SWITCHES: PUBLIC HEALTH IMPLICATIONS

MOLECULAR BASIS FOR THE HUMAN MALARIA TOLL

CHAPTER 6 FROM POPULATION GENOMICS TO ELUCIDATED TRAITS IN PLASMODIUM FALCIPARUM

POPULATION STRUCTURE

LINKAGE DISEQUILIBRIUM (LD)

DIVERSITY AND DIVERGENCE

GWASs

APPLICATION OF GWAS TO DRUG RESISTANCE

ELUCIDATED TRAIT FOR DRUG RESISTANCE DISCOVERED USING GWAS

SUMMARY POINTS

CHAPTER 7 SELECTIVE SWEEPS IN HUMAN MALARIA PARASITES

INTRODUCTION

TYPES OF SELECTION

HITCHHIKING

COMMON GENETIC VARIATIONS IN MALARIA PARASITES

DRUG SELECTIVE SWEEPS IN P. FALCIPARUM

CONCLUSION

ACKNOWLEDGMENTS

CHAPTER 8 EVOLUTION OF DRUG RESISTANCE IN FUNGI

THE MAJOR ANTIFUNGAL CLASSES AND THEIR MODE OF ACTION

ADAPTIVE MECHANISMS

NATURAL VARIATION IN RESISTANCE TO ANTIFUNGAL DRUGS

EVOLUTION OF DRUG RESISTANCE IN THE HUMAN HOST

EXPERIMENTAL EVOLUTION OF DRUG RESISTANCE

THWARTING THE EVOLUTION OF DRUG RESISTANCE

HOST MODEL SYSTEMS FOR DRUG SCREENING

CONCLUSION

CHAPTER 9 DISCOVERY OF EXTANT SEXUAL CYCLES IN HUMAN PATHOGENIC FUNGI AND THEIR ROLES IN THE GENERATION OF DIVERSITY AND VIRULENCE

MATING IN C. NEOFORMANS

SAME-SEX MATING IN CRYPTOCOCCUS

THE ADVANTAGES OF UNISEXUAL MATING IN CRYPTOCOCCUS SPECIES

MATING AND PATHOGENESIS IN C. NEOFORMANS

MATING IN ASPERGILLUS SPECIES

DISCOVERY OF A SEXUAL CYCLE IN A. FUMIGATUS

MATING AND DISEASE IN ASPERGILLUS

MATING IN CANDIDA SPECIES

THE WHITE-OPAQUE PHENOTYPIC SWITCH

C. ALBICANS SAME-SEX MATING AND THE PARASEXUAL CYCLE

SEXUAL REPRODUCTION IN OTHER CANDIDA SPECIES

MATING AND PATHOGENESIS IN CANDIDA

SEX IN OTHER HUMAN FUNGAL PATHOGENS

SEX AND FUNGAL PATHOGENS: A BROADER VIEW

ACKNOWLEDGMENTS

CHAPTER 10 WORLDWIDE MIGRATIONS, HOST SHIFTS, AND REEMERGENCE OF PHYTOPHTHORA INFESTANS, THE PLANT DESTROYER

INTRODUCTION

EMERGENCE OF LATE BLIGHT IN THE UNITED STATES AND EUROPE

EVOLUTIONARY POSITION AND PHYLOGENETIC RELATIONSHIPS OF PHYTOPHTHORA SPP.

LIFE HISTORY OF THE PATHOGEN

POPULATION BIOLOGY: MIGRATION THEORIES OF P. INFESTANS IN THE 19TH CENTURY

WHAT mtDNA HAPLOTYPE CAUSED THE FAMINE AND WHERE DID IT COME FROM?

WHEN DID THE mtDNA HAPLOTYPE Ib MIGRATE FROM SOUTH AMERICA?

HISTORIC MIGRATIONS: “OUT-OF-SOUTH AMERICA” MIGRATION HYPOTHESIS

HOST SHIFTS AND JUMPS

WHY IS LATE BLIGHT A REEMERGING DISEASE?

CONCLUSIONS

CHAPTER 11 EXPERIMENTAL AND NATURAL EVOLUTION OF THE CRYPTOCOCCUS NEOFORMANS AND CRYPTOCOCCUS GATTII SPECIES COMPLEX

INTRODUCTION TO THE CRYPTOCOCCUS NEOFORMANS SPECIES COMPLEX (CNSC)

GENETIC REQUIREMENTS FOR VIRULENCE

ANALYSES OF NATURAL POPULATIONS OF THE C. NEOFORMANS SPECIES COMPLEX

MICROEVOLUTION DURING INFECTION

EXPERIMENTAL EVOLUTION STUDY OF HIGH TEMPERATURE GROWTH AND IMPLICATIONS FOR LIFE HISTORY EVOLUTION IN HUMAN PATHOGENS

RELATIONSHIP BETWEEN SEX AND VIRULENCE

CONCLUDING REMARKS

CHAPTER 12 POPULATION GENETICS, DIVERSITY, AND SPREAD OF VIRULENCE IN TOXOPLASMA GONDII

IMPORTANCE

VARIABLE CLINICAL OUTCOMES

PHYLOGENETIC CONTEXT AND TYPICAL TRANSMISSION MODES

REMARKABLE TRANSMISSION MODALITIES FOR T. GONDII

CLONAL AND SEXUAL PROPAGATION

ACUTE INFECTION AND VIRULENCE IN THE MOUSE MODEL

CHRONIC INFECTION, BEHAVIOR, AND MORBIDITY

FUTURE PROSPECTS

PART III: FORWARD AND REVERSE GENETIC SYSTEMS FOR DEFINING VIRULENCE

CHAPTER 13 GENETIC CROSSES IN PLASMODIUM FALCIPARUM: ANALYSIS OF DRUG RESISTANCE

INTRODUCTION

THE CLASSICAL GENETICS APPROACH

MAPPING MAJOR GENE EFFECTS

MULTIGENIC TRAITS AND QTL MAPPING

CLASSICAL GENETICS IN THE ERA OF DATA-DRIVEN SCIENCE

SUMMARY

CHAPTER 14 GENETIC MAPPING OF VIRULENCE IN RODENT MALARIAS

THE MURINE RODENT MALARIA PARASITES

THE DEFINITION OF VIRULENCE IN MALARIA

APPROACHES TO THE STUDY OF VIRULENCE IN MALARIA

APPROACHES TO THE GENETIC INVESTIGATION OF MALARIA PARASITES

THE GENETIC ANALYSIS OF VIRULENCE IN RODENT MALARIA PARASITES

THE RETICULOCYTE BINDING-LIKE PROTEINS (RBLs) OF P. Y. YOELII

HOST FACTORS THAT MODULATE THE VIRULENCE OF P. Y. YOELII PARASITES

SUMMARY

CHAPTER 15 GENETIC MAPPING OF ACUTE VIRULENCE IN TOXOPLASMA GONDII

THE ORGANISM, LIFE CYCLE, AND TRANSMISSION

MOUSE MODEL: STRENGTHS AND LIMITATIONS

THE IMMUNE RESPONSE AND CONTROL OF INFECTION

HOST CELL INVASION AND PROTEIN SECRETION

SUBVERSION OF HOST CELL SIGNALING

EXPERIMENTAL GENETICS

NATURE HAS PROVIDED US WITH HIGHLY INFORMATIVE “VARIANTS”

KEY PARAMETERS AND USES OF THE GENETIC MAP

MAPPING BIOLOGICALLY IMPORTANT PHENOTYPIC DIFFERENCES

ROP18: A POLYMORPHIC PV MEMBRANE PROTEIN THAT INTERSECTS AT LEAST TWO CRITICAL AND DISTINCT HOST PATHWAYS INVOLVED IN THE IMMUNE RESPONSE

ROP16: A TYROSINE KINASE TARGETED TO THE HOST NUCLEUS THAT DRAMATICALLY ALTERS THE CHARACTER OF THE HOST IMMUNE RESPONSE

ROP5: A CRUCIALLY IMPORTANT BUT ENIGMATIC PSEUDOKINASE

GRA15: POLYMORPHIC DENSE GRA PROTEINS CAN ALSO IMPACT THE HOST IN A STRAIN-SPECIFIC MANNER

RELEVANCE TO OTHER HOSTS, TRANSMISSION, AND POPULATION

SUMMARY AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

CHAPTER 16 VIRULENCE IN AFRICAN TRYPANOSOMES: GENETIC AND MOLECULAR APPROACHES

INTRODUCTION

THE VIRULENCE PHENOTYPE

GENETIC BASIS OF VIRULENCE

CONCLUSIONS AND FUTURE PROSPECTS

ACKNOWLEDGMENTS

CHAPTER 17 THE EVOLUTION OF ANTIGENIC VARIATION IN AFRICAN TRYPANOSOMES

INTRODUCTION

WHAT WAS THE ORIGIN OF THE VSG?

HOW DID THE VSG FAMILY BECOME SO LARGE AND DIVERSE AND HOW IS IT EVOLVING AT PRESENT?

ARE THE FEATURES OF T. BRUCEI VSG ANTIGENIC VARIATION APPLICABLE TO ALL TRYPANOSOMES WITH ANTIGENIC VARIATION?

SUMMARY

CHAPTER 18 ANTIGENIC VARIATION, ADHERENCE, AND VIRULENCE IN MALARIA

INTRODUCTION

PfEMP1, CYTOADHERENCE, AND var GENES

THE var GENE REPERTOIRE AND GENOMIC ORGANIZATION OF THE FAMILY

ASSESSING THE var REPERTOIRE

MECHANISMS OF VARIANT ANTIGEN DIVERSIFICATION

EVOLUTIONARY ORIGINS OF var GENES

PfEMP1 PROTEIN STRUCTURE–FUNCTION

VAR2CSA AND PLACENTAL MALARIA

PfEMP1 EXPRESSION IN THE YOUNG, NONIMMUNE, AND IN NONPLACENTAL SEVERE DISEASE

CONTROL OF var GENE TRANSCRIPTION, SWITCHING, AND EPIGENETIC MEMORY

CONCLUSIONS

CHAPTER 19 INVASION LIGAND DIVERSITY AND PATHOGENESIS IN BLOOD-STAGE MALARIA

INTRODUCTION

DISCOVERY OF HIGH AFFINITY PARASITE LIGANDS AND RECEPTORS FOR ERYTHROCYTE INVASION

IDENTIFICATION OF MULTIPLE ERYTHROCYTE RECEPTORS FOR INVASION

DIVERSITY IN SEQUENCE AND EXPRESSION OF PLASMODIUM INVASION LIGANDS DEFINES INVASION PATHWAYS

FUNCTIONAL ANALYSES OF LIGAND–RECEPTOR INTERACTIONS IN PLASMODIUM spp. IN VITRO

BIOLOGICAL CONSEQUENCES OF DIVERSITY IN LIGAND–RECEPTOR INTERACTIONS

IN VIVO PATHOLOGICAL CONSEQUENCES OF DIVERSITY IN LIGAND–RECEPTOR INTERACTIONS

OTHER INVASION LIGANDS INVOLVED IN ALTERNATIVE INVASION PATHWAY UTILIZATION?

CONCLUSIONS AND FUTURE QUESTIONS

PART IV: COMPARATIVE “OMICS” APPROACHES TO DEFINING VIRULENCE

CHAPTER 20 EVOLUTION OF VIRULENCE IN OOMYCETE PLANT PATHOGENS

INTRODUCTION

THE BASIS AND BASICS OF PLANT–PATHOGEN COEVOLUTION

OOMYCETE MAMPs: ACTIVATING THE FRONTLINE OF PLANT DEFENSE

THE EXPANDING OOMYCETE EFFECTOR COLLECTION: SUPPRESSORS OF PTI AND MANIPULATORS OF HOST METABOLISM

CYTOPLASMIC EFFECTORS

ETI TO OOMYCETE PLANT PATHOGENS

BIOTROPHY VERSUS NECROTROPHY: GENOME STUDIES REVEAL THE DIFFERENCES

THE FUTURE: FROM SYSTEMS BIOLOGY TO TRANSLATIONAL RESEARCH

CHAPTER 21 EVOLUTION AND GENOMICS OF THE PATHOGENIC CANDIDA SPECIES COMPLEX

INTRODUCTION: THE ORGANISMS AND THEIR PATHOECOLOGY

GENOME ANALYSIS: C. gLABRATA

GENOME ANALYSIS: CTG CLADE

GENE EXPRESSION DIFFERENCES

MORPHOLOGY AND VIRULENCE

ANALYSIS OF THE MATING PATHWAY

TYPING, POPULATION ECOLOGY, AND EVOLUTION

CONCLUSION

ACKNOWLEDGMENTS

CHAPTER 22 EVOLUTION OF ENTAMOEBA HISTOLYTICA VIRULENCE

INTRODUCTION

GENETIC DIVERSITY

LINK BETWEEN GENOTYPE AND VIRULENCE

VIRULENCE MECHANISMS

SUMMARY, LIMITATIONS, AND OPPORTUNITIES FOR FUTURE WORK

CHAPTER 23 SEX AND VIRULENCE IN BASIDIOMYCETE PATHOGENS

INTRODUCTION TO THE BASIDIOMYCOTA

SMUT FUNGI

CRYPTOCOCCUS SPECIES

RUST FUNGI

SUMMARY

CHAPTER 24 EMERGENCE OF THE CHYTRID FUNGUS BATRACHOCHYTRIUM DENDROBATIDIS AND GLOBAL AMPHIBIAN DECLINES

INTRODUCTION

HOST–PATHOGEN INTERACTIONS AND PATHOGENICITY IN Bd

COMPARATIVE EVOLUTIONARY GENOMICS OF Bd

GLOBAL VECTORS OF Bd

POPULATION GENOMICS OF Bd AND THE ORIGINS OF THE Bd PANZOOTIC

VARIATION IN VIRULENCE AND PATTERNS OF DIVERSITY AMONG LINEAGES OF Bd

SUMMARY POINTS

ACKNOWLEDGMENTS

CHAPTER 25 IMPACT OF HORIZONTAL GENE TRANSFER ON VIRULENCE OF FUNGAL PATHOGENS OF PLANTS

INTRODUCTION

EVIDENCE USED TO SUPPORT THE OCCURRENCE OF HGT

FREQUENCY OF HGT AND PROPOSED MECHANISMS OF TRANSFER

HGT OF SINGLE GENES

HGT OF CLUSTERS OF GENES ENCODING ENZYMES FOR BIOSYNTHESIS OF SECONDARY METABOLITE TOXINS

HORIZONTAL CHROMOSOME TRANSFER

CONCLUSIONS

ACKNOWLEDGMENT

CHAPTER 26 EVOLUTION OF PLANT PATHOGENICITY IN FUSARIUM SPECIES

INTRODUCTION

DETERMINANTS OF PATHOGENICITY WITHIN THE GENUS FUSARIUM

EVOLUTION OF PATHOGENICITY REVEALED THROUGH FUSARIUM COMPARATIVE GENOMICS

EVOLUTION OF SECONDARY METABOLITE GENE CLUSTERS ASSOCIATED WITH PATHOGENICITY

CONCLUSION

CHAPTER 27 GENETIC, GENOMIC, AND MOLECULAR APPROACHES TO DEFINE VIRULENCE OF ASPERGILLUS FUMIGATUS

INTRODUCTION

CONCLUSION

CHAPTER 28 CRYPTOSPORIDIUM: COMPARATIVE GENOMICS AND PATHOGENESIS

INTRODUCTION

PATHOGENESIS AND VIRULENCE

EVOLUTION, GENOMICS, AND POPULATION STRUCTURE

CHALLENGES AND UNANSWERED QUESTIONS

Index

Front Cover: Top left: Sexual fruiting body of Pyrenophora tritici-repentis the cause of tan spot of wheat (image credit Kasia Rybak). Top right: Immunofluorescence image of intracellular tachyzoites of Toxoplasma gondii, a common opportunistic pathogen of humans (image credit Jennifer Gordon). Bottom left: Zygospore of Mucor circinelloides, a dimorphic fungal plant pathogen (image credit Soo Chan Lee): used with permission PLoS Pathog 7(6): e1002086. Bottom right: Intracellular trophozoite of Plasmodium falciparum, the cause of malaria, within red blood cell (image credit Wandy Beatty).

Back Cover: Top: Electron micrograph of blood stream trypanosomes of Trypanosoma brucei (image credit Wandy Beatty). Bottom: Yeast and hyphal forms of Candida tropicalis (image credit Ying-Lien Chen)

Copyright © 2012 by Wiley-Blackwell. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Sibley, L. David.

 Evolution of virulence in eukaryotic microbes / editors, L. David Sibley, Barbara J. Howlett, Joseph Heitman.

p. cm.

 Includes index.

 ISBN 978-1-118-03818-5 (hardback)

 1. Protista. 2. Eukaryotic cells. 3. Microbial genomics. 4. Virulence (Microbiology)–Genetic aspects. I. Howlett, Barbara J. II. Heitman, Joseph. III. Title.

 QR74.5.S53 2012

 579–dc23

2011051095

PREFACE

This volume assembles for the first time a collection of chapters on the diversity of eukaryotic microorganisms and the influence of evolutionary forces on the origins and emergence of their virulence attributes. In selecting the topics for this volume, we have highlighted examples from three important, divergent groups of eukaryotic microorganisms that cause disease in animals and plants. These include oomycetes, the cause of serious blights in plants, such as the Irish potato famine, protozoan parasites of humans, including Plasmodium, the causative agent of malaria, and fungi that cause diseases in animals and plants. Although phylogenetically diverse in the eukaryotic tree of life, each of these groups has adopted pathogenic lifestyles on plant or animal hosts that often result in serious diseases. Traditionally, studies on these three groups of organisms have been pursued by independent scientific communities. Hence, our goal for this volume is to serve as a bridge that links findings from these disparate communities, resulting in a synthesis of knowledge that voices common themes in evolution and pathogenesis.

The overarching theme of this volume is how pathogenic determinants of eukaryotic microorganisms have evolved in concert with their hosts, often overcoming innate and adaptive immune mechanisms. Host defenses are not prominently featured here as there are many volumes covering these aspects of the host–microbe interaction. Rather, our focus is on pathogenic determinants and evolutionary processes that have shaped microbial pathogen genomes and the resulting complex biology they orchestrate. The initial chapters cover general, broad principles of evolution, phylogenetics, and genetic exchange. In many cases, our appreciation of the virulence traits of pathogens has been driven by genetic approaches, either classical or molecular. Hence, one of the subthemes for the book is how the development of genetic tools has fostered the identification and functional analyses of virulence determinants. An equally important subtheme is how pathogens exchange genetic material in nature, including via classical or modified meiotic processes, horizontal gene transfer, and sexual cycles including those that are cryptic or even unisexual. Since genetic exchange provides the means to shuffle genomes and to acquire new determinants, these processes play a central role in the evolution of virulence. The combined treatment of different inheritance systems highlights common mechanisms of evolutionary adaptations that led to the emergence of the capacity to cause disease in diverse hosts.

In comparison to viral and bacterial pathogens, eukaryotic microorganisms are characterized by large genome sizes, complex biological life cycles, and shared biological features with their hosts. These properties combine to create challenges in studying eukaryotic pathogens, both in the laboratory and in animal and plant models. However, these challenges are counter­balanced by recent advances in genetics, comparative genomics, phylogenetics, and evolutionary analyses that have accelerated progress in defining the molecular basis of virulence in eukaryotic pathogens. In the contributions contained herein, these advances illuminate how coevolution between hosts and pathogens has shaped their interactions and the resulting outcome in terms of pathogenesis. Common themes between different pathogenic microbes are illustrated, providing a broad framework for formulating future studies.

We are grateful to all of the authors for their excellent series of contributed chapters, and we hope that the resulting volume will enrich discussions and even drive novel research on eukaryotic pathogens. As with all such publication ventures, this synthesis across disciplines is an experiment. We welcome you as readers to communicate to us ways in which we may have succeeded and also ways in which the focus of our efforts might be sharpened in possible future editions.

L. DAVID SIBLEYBARBARA J. HOWLETTJOSEPH HEITMAN

ACKNOWLEDGMENTS

We thank Eileen Wojciechowski for outstanding administrative assistance and Cecelia Shertz for editing prowess. We are greatly indebted in particular to Janet Whealen, without whom this volume would not have been possible. More than anyone, Jan was responsible for keeping editors and authors on track and for reminding us of both important formatting aspects and timelines. We thank Dr. Karen Chambers, Editor, Life Science, Wiley-Blackwell, for the initial concept this volume and for helping us navigate the complexity of a large publishing house. We are also grateful to Anna Ehlers and other members of the Wiley-Blackwell editorial team for assistance with compiling the final volume. Finally, we acknowledge each of our families for their forbearance during this project.

CONTRIBUTORS

JAMES W. AJIOKA, PHD, Department of Pathology, University of Cambridge, Cambridge, UK

FRANCISCO J. AYALA, PHD, Department of Ecology and Evolutionary Biology, University of California, Irvine, CA

GUUS BAKKEREN, PHD, Pacific Agri-Food Research Centre, Agriculture and Agri-Food Canada, Summerland, BC, Canada

J. DAVID BARRY, PHD, Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

RICHARD J. BENNETT, PHD, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI

JIM L. BEYNON, PHD, School of Life Sciences, The University of Warwick, Warwick, UK

PAUL R. J. BIRCH, PHD, Division of Plant Sciences, University of Dundee at James Hutton Institute, Invergowrie Dundee, UK

JOHN C. BOOTHROYD, PHD, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA

GERALDINE BUTLER, PHD, UCD School of Biomolecular & Biomedical Science, Conway Institute, University College Dublin, Belfield, Ireland

RICHARD CARTER, PHD, School of Biological Sciences, University of Edinburgh, Edinburgh, UK

ARTURO CASADEVALL, MD, PHD, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY

HSIAO-HAN CHANG, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA

MARY E. COATES, PHD, School of Life Sciences, University of Warwick, Warwick, UK

LEAH E. COWEN, PHD, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

RICHARD CULLETON, PHD, Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

RACHEL F. DANIELS, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA

KIRK W. DEITSCH, PHD, Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY

MANOJ T. DURAISINGH, PHD, Harvard School of Public Health, Boston, MA

JEFFREY D. DVORIN, MD, PHD, Children’s Hospital Boston, Boston, MA

ANANIAS A. ESCALANTE, PHD, Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ

RHYS A. FARRER, BSC, MSC, Department of Infectious Disease Epidemiology, Imperial College, London, UK

MICHAEL T. FERDIG, PHD, Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN

MATTHEW C. FISHER, PHD, Department of Infectious Disease Epidemiology, Imperial College, London, UK

MONICA A. GARCIA-SOLACHE, MD, PHD, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY

NEIL A. R. GOW, PHD, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK

DANIEL L. HARTL, PHD, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA

JOSEPH HEITMAN, MD, PHD, Departments of Molecular Genetics and Microbiology, Pharmacology & Cancer Biology & Medicine, Duke University Medical Center, Durham, NC

JESSICA A. HILL, MSC, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

SAMANTHA J. HOOT, PHD, Seattle Biomedical Research Institute, Seattle, WA

BARBARA J. HOWLETT, PHD, School of Botany, The University of Melbourne, Melbourne, VIC, Australia

CHRISTINA M. HULL, PHD, Department of Biomolecular Chemistry and Department of Medical Microbiology and Immunology, University of Wisconsin, School of Medicine and Public Health, Madison, WI

CHRISTOPHER D. HUSTON, MD, Division of Infectious Diseases, University of Vermont College of Medicine, Burlington, VT

ALEXANDER IDNURM, PHD, Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO

ANDREW P. JACKSON, DPHIL, Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, UK

SATOMI KATO, PHD, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA

JESSICA C. KISSINGER, PHD, Department of Genetics, Institute of Bioinformatics, and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA

H. CORBY KISTLER, PHD, USDA ARS Cereal Disease Laboratory, University of Minnesota, St. Paul, MN

MARTIN KOLISKO, PHD, Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biology, Dalhousie University, Halifax, NS, Canada

EMILIA K. KRUZEL, PHD, Department of Biomolecular Chemistry, University of Wisconsin, School of Medicine and Public Health, Madison, WI

JEAN-PAUL LATGE, PHD, Institut Pasteur, Unité des Aspergillus, Paris, France

WENJUN LI, PHD, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC

JOHN M. LOGSDON, JR., PHD, Department of Biology, University of Iowa, Iowa City, IA

MICHAEL LORENZ, PHD, Department of Microbiology and Molecular Genetics, University of Texas-Houston, Houston, Texas

LI-JUN MA, PHD, College of Nature Sciences, University of Massachusetts, Amherst, MA

ANNETTE MACLEOD, PHD, University of Glasgow, College of Medical, Veterinary and Life Sciences, Glasgow, UK

LIAM J. MORRISON, PHD, University of Glasgow, College of Medical, Veterinary and Life Sciences, Glasgow, UK

LAETITIA MUSZKIETA, PHD, Institut Pasteur, Unité des Aspergillus, Paris, France

DANIEL E. NEAFSEY, PHD, Broad Institute, Cambridge, MA

KIRSTEN NIELSEN, PHD, Department of Microbiology, University of Minnesota, Minneapolis, MN

RICHARD P. OLIVER, PHD, Australian Centre for Necrotrophic Fungal Pathogens, Curtin University, Perth, WA, Australia

PETER R. PREISER, PHD, Division of Molecular Genetics and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore

MARTIJN REP, PHD, Molecular Plant Pathology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

JEAN BEAGLE RISTAINO, PHD, Department of Plant Pathology, North Carolina State University, Raleigh, NC

ANDREW J. ROGER, PHD, Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada

BENJAMIN M. ROSENTHAL, SD, Animal Parasitic Disease Laboratory, Agriculture Research Service, USDA, Beltsville, MD

PARDIS C. SABETI, DPHIL, MD, FAS Center for Systems Biology, Harvard University, Cambridge, MA

ELIZABETH SAVELKOUL, Department of Biology, University of Iowa, Iowa City, IA

STEPHEN F. SCHAFFNER, PHD, Broad Institute, Cambridge, MA

L. DAVID SIBLEY, PHD, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO

ALASTAIR G. B. SIMPSON, PHD, Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biology, Dalhousie University, Halifax, NS, Canada

UPINDER SINGH, MD, Division of Infectious Diseases and Geographic Medicine, Departments of Internal Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA

JOSEPH SMITH, PHD, Seattle Biomedical Research Institute, Seattle, WA

JASON E. STAJICH, PHD, Department of Plant Pathology and Microbiology, University of California, Riverside, CA

WILLIAM J. STEINBACH, MD, Department of Pediatrics and Department of Molecular Genetics and Microbiology, Duke University, Durham, NC

XIN-ZHUAN SU, PHD, Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD

ANDY TAIT, PHD, University of Glasgow, College of Medical, Veterinary and Life Sciences, Glasgow, UK

JOHN C. TAN, PHD, Genomics Core Facility, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN

SARAH K. VOLKMAN, SCD, Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA

THEODORE C. WHITE, PHD, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO

DYANN F. WIRTH, PHD, Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA

JOHN C. WOOTTON, PHD, NCBI, NLM, NIH, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD

JIANPING XU, PHD, Department of Biology, McMaster University, Hamilton, ON, Canada

PART IGENERAL OVERVIEWS

CHAPTER 1

POPULATION GENETICS AND PARASITE DIVERSITY

HSIAO-HAN CHANG, RACHEL F. DANIELS, and DANIEL L. HARTL

MUTATION

Mutation encompasses a wide range of changes from substitution of single nucleotides to relocation of entire segments of chromosomes. Single-nucleotide polymorphisms (SNPs) include transitions and transversions that exchange bases within or across purine and pyrimidine classes. Some nucleotide substitutions can affect the codon for an amino acid without changing the amino acid (a synonymous SNP). When the mutant codon does code for a different amino acid, the SNP is nonsynonymous. Some mutations insert or delete one or a small number of nucleotide bases and shift the reading frame of the translational machinery, causing a usually nonfunctional product to be translated from the RNA transcript.

On a larger genetic scale than single-nucleotide changes, copy number variations (CNVs) are mutations caused by mobile genetic elements like insertion sequences, transposons, or retroelements. Genes can also be duplicated through chromosomal mutations such as transpositions and translocations; like the other types of CNVs, these mutations place genes out of their normal genetic context and away from their normal regulatory elements. The new copies may also be less prone to correction by processes such as gene conversion, leaving them free to accumulate further mutations. A special class of copy number polymorphisms consists of minisatellites and microsatellites with variable numbers of tandem repeats of relatively short stretches of DNA.

Mutation can have significant consequences on populations. For example, the effects of nonsynonymous SNPs and CNVs have been associated with reduced drug sensitivity in Plasmodium falciparum, the apicomplexan parasite that causes most malaria deaths. The implications of these and other types of mutations in popula­tions of P. falciparum and other eukary­otic microbes will be discussed in greater detail in later chapters.

At the beginning of population genetics, the only way to observe mutations was through direct polymorphic evidence: Mendel’s vaunted peas, Kettlewell’s melanic moths, and Galton’s amazing catalog of continuous traits all owed their phenotypic variation to different versions of genes where mutations had caused the organisms to appear different from each other. Increasingly sophisticated techniques such as allozyme (also known as allelic isozyme) and restriction fragment length polymorphism (RFLP) analyses allowed more direct studies of protein and DNA differences between individuals within populations and among species. These early experiments formed the basis for many current theories in population genetics and remain informative to the present day. The recent emergence of cost-effective technologies such as DNA and protein arrays has changed the scale and accelerated the discovery of diversity from single genes or proteins to genomes and proteomes in massively multiplexed studies involving larger numbers of individuals within and among populations. Advances in sequencing technologies have further enhanced the deluge of new data available to researchers. With lowered costs and increased coverage, entire genomes can be sequenced for a complete picture of polymorphic sites across populations and time. Further technological advances like hybrid selection and single-molecule amplification mean that pathogens and other microorganisms—including eukaryotic microbes—that cannot be separated from host material or cultured in sufficient quantities to allow easy sequencing under previous technologies can now be sequenced directly from patients or the environment. These technologies do not rely on culturing systems and offer researchers glimpses of the population genetics of pathogens whose mechanisms of virulence may be intractable for study in model organisms.