The Integrated Study of Infections, Immunology, Ecology, and Genetics
Second Edition
Paul Schmid-Hempel
Emeritus Professor, Institute of Integrative Biology (IBZ) and Genetic Diversity Centre, ETH Zürich, Switzerland
Great Clarendon Street, Oxford, OX2 6DP, United Kingdom
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Preface
Parasites and infectious diseases are everywhere around us and have affected the ecology and evolution of organisms since the early days of life on this planet. In fact, this second edition of Evolutionary Parasitology was finished during the Corona year, 2020. The pandemic brought grief and misery to many people, not to speak of the enormous economic costs. At the same time, this pandemic is an impressive illustration of the pervasive influence of parasitism that affects virtually all aspects of the hosts’ lives. The field of evolutionary parasitology, therefore, cuts across many disciplines for a more comprehensive approach to studying hosts and parasites, to appreciate the mechanisms that guide their interactions and to identify the selective forces that shape their biology.
As before, I am using the generic term ‘parasite’ to cover various other names, such as ‘pathogen’ or ‘parasitoid’, which are more common in fields like medicine or agriculture. However, parasitism is the core ecological relationship towards which all scientific endeavours in the larger field gravitate. This relationship is based on molecular and physiological processes, on probabilities of contacts, on binding between surfaces and specific molecules, but also results in more or less success of either party. Hence, the relationship is also under selection and has evolved and co-evolved over the aeons and still continues to do so. In some cases, we see fast evolutionary changes, as with the rise of antibiotic resistance in bacteria, whereas the conserved nature of some elements in immune defence systems points to their deep ancestry across organisms. Indeed, immune systems are among the most complex natural systems that have evolved and, doubtlessly, parasitism was a major driver along this way. But parasites are not just the passive partners, as their typical organismal simplicity would suggest. Instead,
parasites have evolved mind-boggling mechanisms and strategies to evade, overwhelm, and manipulate their hosts in their own favour—this is even true for viruses that undermine their hosts’ defence systems in amazing ways. Therefore, to unravel these fantastic processes and to clarify the evolutionary reasons for the enormous diversity of host defences and parasite strategies is an endlessly captivating venture.
This is a completely rewritten update of Evolutionary Parasitology. It contains a number of tables that cannot be a comprehensive review of the respective topics. Such an attempt would be close to impossible, given the enormous range of activities in this huge area. Rather, and as in the previous edition, the tables should illustrate typical studies, while giving an impression of the variety of study subjects and approaches. As before, I must also apologize to the plant world that my examples are primarily zoonotic in origin. Similarly, social parasites such as inquiline ants or brood parasites in birds are not considered in much detail. Nevertheless, the principles guiding those host–parasite interactions are also the topics of this book.
Looking back, it is astonishing to see how much has happened in the broader field within the decade since the original book appeared. Three elements contributed in important ways. Firstly, the advance in molecular technologies is breathtaking. What once used weeks, is now done in a day, and at a fraction of the cost. Sequencing technologies, for example, have sparked a new age for virology, allowing an ongoing epidemic to be traced almost in real time. Discoveries based on mechanisms in immune defence systems, such as RNAi or CRISPR–Cas, allow the genotypes of organisms to be changed in unprecedented ways. And with mRNA technology a next
toolbox is already on the horizon that not only makes for a new generation of vaccines but can help to further dissect the mechanisms underlying host–parasite interactions. A second methodical element that has contributed to the advance in the field is the progress in mathematical algorithms and computing power, often lumped together as bioinformatics, that makes it possible to use large amounts of information and to analyse these with improved statistical techniques. Reconstructing the molecular epidemiology of viral diseases is just one of the applications of these powerful methods. Finally, the field has progressed in its concepts, which is the ultimate aim of any scientific exploration. For instance, the early phases of infection have come into focus, as did concepts to predict the outcome of an infection based on measures of host status at certain stages of the process. Clearly, evolutionary parasitology has matured, but it will not end soon— too diverse and intriguing are its subjects, too riveting the study of these, and too important the practical implications for matters of agriculture, conservation biology, medicine, and public health.
The daily work of a scientist often is a very lonesome activity, but the process of doing science is not. Therefore, this book also rests on the work of many others. I have been blessed to meet so many outstanding colleagues and to have the chance to discuss questions at the forefront of their respective fields, all of which has influenced this book perhaps more than is visible. To pick just a few, I am grateful for the extended contacts with Janis Antonovics, Mike Boots, Sylvia Cremer, Dieter Ebert, Steve Frank, Andrea Graham, Andrew Read, Jens Rolff, David Schneider, and many others. David Schneider’s concept of the disease space has been a particularly illuminating addition and is used in this book as a guide through the different sections—in the hope that it will always show the relationship between the underlying mechanisms and the ecologic and evolutionary outcome of a parasitic infection. My own scientific home in the Institute of Integrative Biology (IBZ) has been an enormously fruitful set-
ting over the years; the interactions with the groups of Sebastian Bonhoeffer and Roland Regoes especially helped me to reach out into the theoretical domains. Moreover, good fortune has brought many outstanding students and postdocs to my own research group. Working together on topics of host–parasite interactions has been enriching, and a real pleasure. From the more recent past, I just mention Boris Baer, Seth Barribeau, Mark Brown, Jukka Jokela, Hauke Koch, Joachim Kurtz, Yannick Moret, Kathrin Näpflin, Oliver Otti, Livia Roth, Ben Sadd, Rahel Salathé, Yuko Ulrich, Maze Wegner, Lena Wilfert, without any disregard for all the others that have contributed in many other ways. The administrative and technical help of Rita Jenny, Roland Loosli, Christine Reber from IBZ, and Aria Minder from the Genetic Diversity Centre kept many a burden off my table. Of course, my wife Regula has not only shared the ups and downs during writing, but has also helped in many and important ways, both scientifically and with technical support. Finally, a number of colleagues have volunteered to read through the earlier drafts. I am thus very grateful for the valuable input given by Seth Barribeau, Mark Brown, Austin Calhoun, Roger Kouyos, Elyse McCormick, Andrew Read, Roland Regoes, Bryan Sierra Rivera, Jens Rolff, Ben Sadd, and Logan Sauers. A special thanks goes to Louis du Pasquier who had already helped with the first edition, and whose critical advice was essential for the discussion of immune defences. The remaining errors are, of course, mine. Last but not least, I thank Ian Sherman and Charles Bath from Oxford University Press for their generous support and unobtrusive coverage of the entire process. May the efforts aid the field of evolutionary parasitology and advance our scientific understanding of nature.
PaulSchmid-Hempel November 2020
ETH Zürich, Institute of Integrative Biology (IBZ), and Genetic Diversity Centre at ETH, Switzerland
3.2.5
3.4.4
3.4.5
3.4.6
4.2.2
4.2.2.1
4.5.1
4.6.1
4.6.2
5.2.3
5.2.4
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Box
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14
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15.2.1
List of common acronyms
AcronymNameDescription
AGOArgonautBinds to short RNA (siRNA) in the antiviral defence of invertebrates.
AIDActivation-induced cytidine deaminase
Enzyme involved in gene conversion, somatic hypermutation, class switching.
AIDSAcquired immune deficiency syndrome Disease caused by HIV.
AMPAntimicrobial peptideEffector protein with antimicrobial activity.
APCAntigen-presenting cellCells that can bind to and present parasite peptides to passing, for example, CD4+ T-cells.
CD4+, CD8+T-cell with CD4, CD8 proteinHelper cells.
PO; proPOPhenoloxidaseKey enzyme in the defence cascade of arthropods; precursor to PO.
PRRPattern-recognition receptorBinds to general molecular patterns (epitopes), e.g. on bacterial cell walls.
QTLQuantitative trait locusA genetic locus statistically associated with a phenotypic trait.
RAGRecombinase-activating geneInvolved in somatic recombination of genetic elements for lymphocytic receptors.
RelishRelishTranscription factor, e.g. activated by the Toll pathway in insects.
RISCRNA-induced silencing complex Protein complex binding and cleaving RNA strands. Part of the antiviral defence of invertebrates.
RNAiInterference RNAA system that silences genes by degrading the transcribed RNA. Antiviral defence in invertebrates.
ROSReactive oxygen speciesNon-saturated oxygen molecules with high reactivity; toxic for microbes.
SARSSevere acute respiratory syndrome Disease caused by SARS-CoV-1 virus.
SIRSusceptible–infected–recovered Refers to standard model of epidemiology.
SNPSingle-nucleotide polymorphism Variation at a single nucleotide position in a population.
SRScavenger receptorReceptors that trigger removal of modified molecules (lipids) from the cell, but also have immune functions.
TCRT-cell receptorA receptor on the surface of a T-cell, e.g. the CD4 protein.
TEPThioester-containing proteinA class of phagocytic opsonization factors in insects.
TGIPTransgenerational immune priming The phenomenon that offspring of challenged (parasiteexposed) parents are better protected.
Th1, Th2T-helper cells type 1, type 2Helper cells that produce various cytokines, involved in defence against bacteria and viruses (Th1) and helminths (Th2).
TLRToll-like receptorA family of key receptors in the innate immune system.
TNFTumor necrosis factorMembrane-bound cytokine of the immune defence, e.g. inflammation, but also with many other functions.
VLRVariable lymphocyte receptorReceptors at the surface, e.g. on B-cells.
VSGVariable surface glycoproteinsPolymorphic surface molecules (epitopes) recognized by the immune system, e.g. in trypanosomes.
Glossary
Adaptive immunity Immune defence that adapts to ongoing infections by becoming more specific and stronger.
Aetiological agent The agent (parasite) causing a particular disease. For example, HIV causes AIDS.
Affinity Strength of binding, usually between receptor and ligand.
Affinity maturation The process by which B-cells that bind more strongly to a given parasite (antigen) become more common, based on somatic hypermutation.
Allele An alternative variant of a gene at a given locus.
Allograft A foreign tissue that is transplanted onto (or comes in contact with) a host individual.
Alternative splicing A process during gene expression that results in different mRNAs and proteins derived from a single gene.
Anergic An immune cell (lymphocyte) that is unresponsive to an antigen.
Antagonistic pleiotropy Pleiotropic genes affect several phenotypic characters. Antagonistic pleiotropy is often used for a gene that has a positive effect early in life but a negative effect late in life.
Antibiotic resistance Acquired resistance of microbes to antibiotic agents. Also known as antimicrobial resistance, or drug resistance.
Antibody A secreted immunoglobulin (Ig) that binds to a parasite epitope.
Antigen A parasite molecule (or other foreign substance) that stimulates an immune response.
Antigen-presenting cells (APC) A heterogeneous group of immune cells that process and present parasite molecules (antigens) at their surface for other immune cells.
Antigenic drift A change in the antigenic properties of a parasite that results from mutation accumulation in a population, e.g. in an infecting viral population.
Antigenic shift A change in the antigenic properties of a parasite that results from the expression of different stored variants of the individual parasite, or by recombination among different co-infecting strains of viruses, for example.
Antigenic variation Scheduled or random variation of recognized molecules on the surface of parasites (epitopes) to evade the host immune system.
Antimicrobial peptide (AMP) A short protein (peptide) that is able to destroy a (microbial) parasite. Also effective against protozoans. AMPs differ in the exact mechanism of how they damage the parasite. AMPs are effectors of the innate immune system.
Apoptosis Programmed cell death.
Attenuation The process of a parasite losing virulence over generations.
Bacteriocin Molecules produced by bacteria to suppress competing bacteria.
Basic reproductive number, R0 This is the number of newly infected hosts resulting from one already infected host in a population of all susceptible hosts.
Bateman’s principle The observation that males vary more in their reproductive success than females.
Biofilm A dense aggregation of bacteria embedded in a matrix of biopolymers.
Bridge host Used in the study of zoonoses to characterize a host that mediates between background reservoir and the target species.
Candidate gene A gene that is suspected to play a role in a given function. For example, the peptidoglycan recognition genes are very likely to act as recognition molecules for certain kinds of pathogens.
Case mortality rate Mortality rate per diagnosed case, i.e. the probability of host death once infected.
Central tolerance (Immunological) The establishment in lymphocytes of tolerance towards own tissues during maturation of the B- and T-cell populations in the primary lymph organs.
Chemokine A chemical attractant, a molecule, in the immune defence system.
Class switching A process during which an immunoglobulin (antibody) changes its class, e.g. converts from an IgD to an IgE type.
Clearance The process by which the parasite is removed (cleared) from the host; the host becoming uninfected again.
Clonal expansion The process during which B- and T-cells of the vertebrate adaptive immune system multiply in numbers (and mature) to fight a specific infection.
Co-infection Often used to denote the infection of a host by more than one different parasite species or by otherwise very different types. Also more commonly used as a generic term meaning multiple infection by different parasite species or variants.
Coalescence The convergence of two phylogenetic lines at some time in the past.
Constitutive defence A defence that is present and active even before an infection. It can therefore act immediately, should an infection occur.
Copy number variation Variation in the number of copies of a gene within a genome.
Critical community size (Epidemiology) Critical population size to endemically maintain an infectious disease.
Cytokine A signalling protein for immune cells. Helps to orchestrate the immune response.
Cytokine storm An unregulated, massive release of cytokines.
Cytoskeleton The internal skeleton of a cell that allows it to keep and change shape or to move. A highly dynamic structure consisting of protein filaments and microtubules.
Cytosol The fluid components of the plasma inside a cell.
Defensins A class of small cysteine-rich cationic antimicrobial peptides (15–20 residue). They are found in all animals and some higher plants.
Dendritic cell (DC) A type of haemocyte that patrols the body and is able to present antigens (in a MHC–peptide complex) to passing helper T-cells.
Deuterostomes Animals that develop through a ‘mouth second’ scheme, i.e. the first opening of the embryo becomes the anus, and the mouth develops from a sperate opening. These includes a few advanced invertebrate groups, such as the echinoderms, and the chordata, including the vertebrates.
Digenic A parasite having two hosts in its life cycle. Sometimes this term also covers three and more hosts.
Synonym: dixenic.
Dioecious Male and female parasites use different host species (e.g. in some Strepsiptera).
Dixenous Having two hosts, or a host and a vector in the life cycle.
Domain (protein) A domain in a protein is a region with a conserved amino acid sequence and thus of tertiary structure, which defines its function.
Dose The number of parasite cells, cysts, etc. needed to cause a response to infection.
Drift (genetic) With drift, alleles and genotypes are lost by chance, the effect being stronger in small populations.
Drug resistance The same as antibiotic resistance.
Dysbiosis Loss or change of the normal structure (and/or microbes) of the microbiota.
Effective population size Population size that, in terms of population genetics, functions like a standard outbred, diploid population.
Effector Any molecule or process at the end of the immune response cascade that actually affects the parasite. Examples are antimicrobial peptides, encapsulation, cytotoxic lymphocytes.
Emerging disease An infectious disease, not present before, that appears in a host population. Typically, by transfer from a reservoir.
Encapsulation An important effector mechanism in invertebrate immune systems. A parasite thereby gets surrounded by melanizing haemocytes; eventually the parasite is completely enclosed in a sealed capsule and becomes killed.
Endemic A persistent infection in a population in the absence of novel infections coming from the outside.
Endemic threshold Minimum host population size to endemically maintain an infection.
Endocytosis Ingestion of macromolecules by specialized cells such as macrophages.
Endotoxins Compounds associated with the pathogen itself, e.g. located on the bacterial cell, and which cause damage to the host while helping the parasite to infect or spread.
Epidemic An infection in a population that shows a dynamic course starting from a few cases, e.g. a new infection that is spreading.
Epidemiology The study of host–parasite dynamics with population biology and population genetics. In medicine, ‘epidemiology’ is a field that identifies statistical associations between the occurrence of disease and putative causal factor.
Epistasis An effect on the phenotype (e.g. the fitness of an organism) that is due to the particular combination of genes (alleles) at two (digenic epistasis) or more loci. More strictly defined as the deviation in fitness from an additive effects model due to combination of genes.
Epitope A molecular pattern on the surface of a parasite that is recognized by a receptor or ligand of the host.
ESS (Evolutionarily stable strategy) A strategy that, if adopted by all individuals in the population, cannot be invaded by a rare mutant.
Exon Any part of a gene that is finally transcribed into mRNA.
Exotoxin Proteins released by a pathogen such as a bacterium and which can take effect far from the site of infection.
Extant Still existing today, e.g. a currently living species.
Fecundity In ecology, the average per capita number of offspring in a population.
Final (definitive) host For a parasite with several hosts in its life cycle, the final host is judged to be the most ‘important’. Often this is the host where the parasite sexually reproduces, but this is not always so.
Force of infection The rate at which an exposed uninfected individual becomes infected by transmission from infected hosts. In a mass action model (such as in the standard SIR model), this is proportional to the product of the number of infected individuals and transmission rate (i.e. infection probability per encounter).
Gene conversion A process that happens during a (homologous) recombination event where the ‘donor’ gene remains the same but the ‘receptor’ gene acquires the recombined sequence. This leads to an altered gene; i.e. the gene has converted into a new one.
Genome The entire genetic sequence of an organism.
Genomics The study of genomes.
Gram-negative bacteria A heuristic category for bacteria that appear red or pink after the Gram stain process and subsequent safranin treatment. Gram-negative bacteria have two membranes—a thin peptidoglycan layer and an outer layer of lipopolysaccharides—separated by the periplasmic space.
Gram-positive bacteria A heuristic category for bacteria that appear blue or violet during the Gram staining process. Gram-positive bacteria have a thick cell wall but only one membrane layer.
Haematopoiesis Cell development (of immune cells).
Haemolymph The circulating body fluid in insects (or arthropods more generally); the ‘blood’ of insects.
Helper T-cell Same as CD4+ T-cell. Functions to provide a signal necessary to stimulate the antibody or cytotoxic lymphocyte response (CTL).
Herd immunity A population is protected from an infectious parasite by herd immunity when a critical fraction of the population can no longer become infected, e.g. by vaccination. The effect results from the epidemiological dynamics of host–parasite interactions so as to lower the basic reproductive rate of the parasite to a value less than one.
Heterologous immunity Immunity directed against a different (heterologous) parasite than what originally caused it.
Heteroxenic In parasite life cycles: using different host species.
Horizontal (gene) transfer (Lateral gene transfer) The transfer of genes from one phylogenetic line or species to another. Different processes can be involved.
Horizontal transmission The transmission of parasites between hosts of the same population and generation. i.e. not to own offspring.
Host range The list of host species used by a parasite. Sometimes called ‘host spectrum’.
Host reservoir Where an infection usually resides endemically and away from the host under scrutiny.
Hypermutation A process of somatic mutation in vertebrate adaptive immunity where mutation rates are increased during the maturation of lymphocytes.
Hypersensitive response In plants: a non-specific, early and fast immune response. It is characterized by a rapid induction of apoptosis in cells around the infection site. An oxidative burst occurs.
Immune priming Used to denote the phenomenon of an immune memory in invertebrates.
Immunocompetence The capacity to mount an immune response to a challenge. Sometimes also defined more loosely as the ability to withstand infection and disease. Originally considered to be a summary measure for all possible immune responses.
Immunodominance A response dominated by a few epitopes, triggering affinity maturation.
Immunogen A stimulus, such as a foreign object or substance, able to trigger an immune response.
Immunoglobulin (Ig) Globulins in serum with antibody activity. There are five major classes: IgG, IgM, IgA, IgE, IgD.
Immunological tolerance A process during the maturation of lymphocytes whereby self-reactive cells are eliminated or modified.
Immunopathology Pathological effects caused by the immune system itself.
Incubation period Time from infection to first signs of the disease.
Index case The first identified case (i.e. infected host) in an epidemic.
Induced defence A defence that is activated upon infection. The defence therefore needs to be built up before it can take an effect.
Infective dose Dose needed to start an infection.
Inflammasome A large, cytosolic protein complex formed during inflammation.
Inflammation An early, innate immune defence where immune cells such as macrophages or monocytes are recruited (by cytokines) to the site of infection.
Innate immunity A collection of diverse defence systems in all animals or plants, e.g. phagocytosis, complement, or TLR pathways. Essentially based on germline-encoded molecules with no specific somatic modifications.
Inoculum The population of parasites used for (experimentally) infecting a parasite. From the Latin word ‘inoculare’ (‘to graft a scion’).
Integument The outer shell of an animal’s body. Examples are the mammalian skin or the insect cuticles.
Intensity (infection) The number of parasite cells or parasite individuals within a given host individual (parasite load, parasite burden).
