Evolutionary Medicine
Preface
Road map
Other books
Thoughts for instructors
Chapter 1: Introduction
Natural selection The four necessary conditions Variation in reproductive success Variation in traits The correlation of traits with reproductive success Variation must have a genetic basis An example: Antibiotic resistance Other cases of medical importance Summary
Neutral evolution The genetic code is redundant Some amino acid substitutions do not change protein function Canalization buffers phenotypes against genetic and environmental changes Tradeoffs cause fitness compensation among traits
Mechanisms causing random change The sense in which mutations are random Effects of small populations Meiosis is a faircoin Genes drift when they land at random in families of different sizes The molecular clock seen in influenza samples Summary
Mismatch Mismatch in time and space Traits are adapted to things that happen frequently Summary
Adaptation Observing natural selection Perturbing the trait Producing the trait only when it serves a function The design criterion Resisting invasion Summary
Styles of thought Typological thinking Population thinking Tree thinking Summary
Chapter 2: What Is a Patient?
Ancient histories with medical consequences Asymmetric division: the condition for the evolution of aging Most cancers originate in stem cells A transposon insertion enabled the vertebrate adaptive immune system Invasive placentas occur in lineages with risk of metastasis The transition to bipedal locomotion led to problems giving birth Summary
Recent history generating diversity Migration out of Africa Genetic evidence on recent human evolution Support for the concept of race is weak Summary
Variation in disease resistance GWAS using SNPs Sequencing approaches Genes with large effects Genes with moderate effects Genes with small effects The impact of variation in the pathogen Summary
Variation in drug metabolism Variation in Cytochrome p450s Variation in n‐acetyl transferases Individual reactions to chemotherapy Using GWAS to discover genetic variation for drug response Summary
Variation in life history traits Age and size at maturity Phenotypic plasticity for maturation in humans Summary
Plasticity and reaction norms Reaction norm basics Genetic correlations among traits are plastic The medical significance of phenotypic plasticity Summary
Tradeoffs Tradeoffs as energy allocations Where do tradeoffs occur, and what causes them? Is there a tradeoff between reproduction and survival in humans? Hormones and the tradeoff between growth, reproduction, and immune function Do tradeoffs evolve? The case of compensatory mutations Deviations from “normal” are unavoidable and often have costs Summary
Aging Some background The key assumptions of the evolutionary theory of aging The causes of aging Why the body is disposable Who should age? Are any organisms potentially immortal? What mechanisms mediate aging? Could humans be selected to live longer? Summary
The unusual human life history Oocytic atresia and selective spontaneous abortions Size at birth: Where many tradeoffs start Growth patterns Patterns of reproductive investment Lifespan and aging Menopause Summary
Developmental origins of health and disease Two early hypotheses: Thrifty genotypes and thrifty phenotypes The Dutch Hunger Winter The effects of pregnancy‐related stress under more normal conditions Is the response adaptive? Summary
The microbiota and their microbiome Co‐development: Evidence of co‐evolution Delivery method affects disease risk Breast feeding affects disease risk Antibiotic treatments increase the risk of atopies and obesity Geographic comparisons of populations Summary
So what is a patient?
Chapter 3: What Is a Disease?
Introduction Four perspectives on human diseases Diseases have both mechanistic and evolutionary explanations
Genetic and environmental causation are each of two types Gene–environment interactions: GxE Causation Summary
Organs and tissues: From vulnerable to robust Tissue renewal and repair Sensitivity to stress Vulnerability to threats The weakest physiological links Built‐in safety factors Tradeoffs and constraints explain vulnerability Tradeoffs and mismatch: When large benefits can carry large costs Summary
From fixed to adjustable Summary
The changing nature of disease Monogenic and stochastic developmental diseases Environmental diseases Summary
Chapter 4: Defenses
Maintenance and defense originated in homeostasis Distinctions among the three processes Two types of maintenance mechanisms Inducible versus constitutive processes Summary
Types of defense and costs The nature of environmental hostility Defenses have costs: They participate in tradeoffs The structure of the costs of defense How defenses lead to disease When do costs become unacceptable? When do defenses cause disease? When should symptoms be treated? Summary
Specialized defenses Starvation Dehydration and volume depletion Cold and heat stress Hypoxia The fight or flight response Pain (nociception) Tissue repair and blood clotting Inflammatory response Allergic defenses The detoxification response The immune response to infection Diseases of exaggerated defense Summary
Key characteristics of defenses Constitutive versus inducible Hormesis and acclimation Time scales of deployment Similarities in immune and behavioral defenses The benefits and costs of flexibility and homeostasis Redundancy, compensation and compatibility of defenses Summary
Defense Strategies: Avoidance, resistance, and tolerance Conceptualizing resistance and tolerance Defense and physiological priorities Failure of tolerance can contribute to infectious disease mortality A classic case of tolerance: SIV in its natural hosts Tolerance has its own costs Summary
Evolution of immunity The innate immune system The adaptive immune system Clonal selection Immune defense and its costs Summary
Chapter 5: Pathogen Evolution
Virulence caused by pathogens The virulence‐transmission trade‐off Vertical versus horizontal transmission Single versus multiple infection One versus many host species Spillover virulence in facultative opportunists The effect of human interventions on pathogen virulence Imperfect vaccines and virulence Summary
Managing the microbiome: Symbionts versus pathogens The gut ecosystem The skin ecosystem Extrinsic and intrinsic virulence Tolerance, resistance, and susceptibility: The lessons of rinderpest Summary
Evasion and suppression of the immune system Immune suppression by viruses Variation of surface properties by bacteria Bacteria that hide inside cells Toxoplasma, a single‐celled eukaryotic pathogen, hides in cysts Plasmodium confronts and solves problems in two hosts Trypanosomes, the classical case of antigenic variation Immune suppression Summary
The rapid evolution of antibiotic resistance What are antibiotics, and how do they work? How do resistance genes get into patients? Bacterial genetics have implications for therapy Why does resistance evolve quickly and spread widely? How can we delay, avoid, or prevent the evolution of antibiotic resistance? Summary
Therapies that mitigate evolutionary consequences Slowing resistance evolution by managing therapy Phage therapy Disrupting bacterial production of public goods Summary
Chapter 6: Cancer
Introduction Types of cancer Hallmarks of cancer Cancer prevalence Why humans are especially susceptible to cancer Summary
Why we are susceptible The causes and consequences of aging The multicellular covenant and the double‐edged sword of stem cells Are there really genes “for” cancer? Somatic mutations and cancer: Heterogeneous risk Summary
Every cancer is an instance of clonal evolution Neoplasms evolve by natural selection Clonal evolution has some special features Summary
Cancer phylogenetics The problem of genetic heterogeneity Using phylogenies to evaluate preventive therapies Summary
Immune evasion and suppression Dealing with a major enemy: NK cells Exploiting a chink in the armor: protection against autoimmunity Modifying metabolism to create an advantage for cancer Summary
Evolved resistance to chemotherapy Targeted immunotherapy Evolutionary approaches Summary
Chapter 7: Reproductive Medicine
The evolution of mammalian reproduction The evolutionary developmental genetics of multicellular eukaryotes The evolution of the female reproductive system One mechanism involved in the innovations: transposon insertion Summary
The evolution of invasive placentas Placental morphology The history of placental layers and shapes Placental morphology and risk of pre‐eclampsia Placental invasiveness and risk of metastasis Summary
Parent–offspring conflict and genomic imprinting The basic idea of kin‐selection The basic idea of parent–offspring conflict Parent–offspring conflicts in pregnancy Evolutionary conflicts and genomic imprinting Evolutionary conflicts and mental disorders Summary
Menstruation The comparative biology and evolutionary history of menstruation Summary
Menopause Summary
Upright posture and childbirth Childbirth is risky Human bipedalism and brain size combine to make birth difficult Summary
Chapter 8: Mismatch
Introduction The importance of relative rates The many consequences of human niche construction Dysevolution and the mismatch diseases The different consequences of undirected, unpredictable environmental and cultural change The roles of microbiota in human health
The major cultural and epidemiological transitions
The message of lactase persistence
Mismatches in space
Obesity, a condition with many causes Energy balance: Too much food, too little exercise Sleep deprivation and ghrelin Breast feeding and caesarean sections Abnormal weight early in life
Type 2 diabetes
Cardiovascular disease
Female reproductive cancers
Hygiene, Old Friends, asthma, and autoimmune diseases Correlations between parasite exposure, atopies, and autoimmune diseases How might worms be interacting with the immune system? Worm therapy is a risky tradeoff Clinical trials of worm therapy have not yet been successful Summary
Conclusion
Chapter 9: Mental Disorders
Introduction The special difficulties of explaining mental disorders A null hypothesis How evolution might enter the picture Mental disorders as byproducts of defense systems Mental disorders as diseases of homeostasis and mismatch
Drug addiction The innate reward and pain‐suppression systems Hijacking the reward system Self‐medicating with plant compounds Genetic variation in susceptibility to addiction Summary
Anxiety, depression, and obsessive–compulsive disorders Anxiety The smoke detector principle and the null hypothesis of complex systems Depression Obsessive–compulsive disorder Summary
Autism and schizophrenia Meta‐analysis using copy‐number variation Size at birth as a marker of risk of mental disorders Summary
Chapter 10: Individual versus Population Health
Introduction
Population consequences of medical decisions Vaccination Antibiotic Therapy How to weigh the good of the individual against the good of the population? Summary
The Great Transition and natural selection How declines in mortality and fertility are changing selection The impact of changed selection on life history evolution Longevity and antagonistic pleiotropy Summary
The Great Transition: Nutrition, energetics, and fertility
The shift from infectious to degenerative disease Summary
Chapter 11: Open Questions and Other Issues
Introduction
Open questions Can we develop evolution‐proof antimicrobial therapies? Can we switch the host–pathogen interaction from resistance to tolerance? Does virulence evolve when leaky vaccines are used? Can we treat cancer by slowing somatic evolution? What are the ultimate reasons for susceptibility to cancer? Do early–late life history tradeoffs suggest treatments for aging? What is the role of parent‐of‐origin imprinting in mental disease? Summary
Why some issues were not addressed Life history evolution does not predict intelligence or criminality Much of what is written about paleodiets is bad science Summary
Differences between classical and evolutionary medicine Summary
References