Contents
Evolution by Natural Selection 73 3.1 Artificial
Selection: Domestic Animals and Plants 74 3.2
Evolution by Natural Selection 77 3.3 The Evolution of Flower Color in an Experimental Snapdragon
Population 79 3.4 The Evolution of Beak Shape in
Galápagos Finches 81 Computing Consequences 3.1
Estimating heritabilities despite complications 84 3.5
The Nature of Natural Selection 90 3.6 The Evolution of Evolutionary Biology 94 3.7 Intelligent Design
Creationism 97 Summary 104 • Questions 105
Exploring the Literature 106 • Citations 106 CHAPTER
4 Estimating Evolutionary Trees 109 4.1 How to Read an Evolutionary Tree 110 4.2 The Logic of Inferring
Evolutionary Trees 114 4.3 Molecular Phylogeny
Inference and the Origin of Whales 123 Computing
Consequences 4.1 Calculating the likelihood of an evolutionary tree 129 Computing Consequences 4.2
Neighbor joining: A distance matrix method 130
Preface ix PART 1 INTRODUCTION 1 CHAPTER 1 A
Case for Evolutionary Thinking: Understanding HIV 1
1.1 The Natural History of the HIV Epidemic 2 1.2 Why Does HIV Therapy Using Just One Drug Ultimately Fail?
9 1.3 Are Human Populations Evolving as a Result of the HIV Pandemic? 15 1.4 Where Did HIV Come From?
18 1.5 Why Is HIV Lethal? 23 Computing
Consequences 1.1 When did HIV move from chimpanzees to humans? 24 Summary 31 • Questions 31 Exploring the Literature 32 • Citations 33 CHAPTER
2 The Pattern of Evolution 37 2.1 Evidence of Microevolution: Change through Time 39 2.2 Evidence of Speciation: New Lineages from Old 44 2.3 Evidence of Macroevolution: New Forms from Old 49 2.4
Evidence of Common Ancestry: All Life-Forms Are Related 55 2.5 The Age of Earth 62 Computing
Consequences 2.1 A closer look at radiometric dating 65 Summary 66 • Questions 67 Exploring the
Literature 68 • Citations 69 iv 4.4 Using Phylogenies to Answer Questions 137 Summary 141 • Questions 141
Exploring the Literature 143 • Citations 143 PART 2
MECHANISMS OF EVOLUTIONARY CHANGE 147
CHAPTER 5 Variation Among Individuals 147 5.1 Three Kinds of Variation 148 Computing Consequences 5.1
Epigenetic inheritance and evolution 154 5.2 Where New Alleles Come From 157 5.3 Where New Genes
Come From 161 Computing Consequences 5.2
Measuring genetic variation in natural populations 162 5.4 Chromosome Mutations 166 5.5 Rates and Fitness
Effects of Mutations 169 Summary 174 • Questions
175 Exploring the Literature 176 • Citations 176
CHAPTER 6 Mendelian Genetics in Populations I: Selection and Mutation 179 6.1 Mendelian Genetics in Populations: Hardy–Weinberg Equilibrium 180 Computing Consequences 6.1 Combining probabilities 185 Computing Consequences 6.2 The Hardy– Weinberg equilibrium principle with more than two alleles 189 6.2 Selection 191 Computing
Consequences 6.3 A general treatment of selection 194 Contents v Computing Consequences 6.4
Statistical analysis of allele and genotype frequencies
using the r2 (chi-square) test 198 Computing
Consequences 6.5 Predicting the frequency of the CCR5-632 allele in future generations 201 6.3 Patterns of Selection: Testing Predictions of Population
Genetics Theory 201 Computing Consequences 6.6
An algebraic treatment of selection on recessive and dominant alleles 204 Computing Consequences 6.7
Stable equilibria with heterozygote superiority and unstable equilibria with heterozygote inferiority 208
6.4 Mutation 216 Computing Consequences 6.8 A mathematical treatment of mutation as an evolutionary mechanism 218 Computing Consequences 6.9 Allele frequencies under mutation–selection balance 220 Computing Consequences 6.10
Estimating mutation rates for recessive alleles 222 6.5
An Engineering Test of Population Genetics Theory 224
Computing Consequences 6.11 Predicting the frequency of Medea across generations 226 Summary 227 • Questions 227 Exploring the Literature 229 •
Citations 231 CHAPTER 7 Mendelian Genetics in Populations II: Migration, Drift, and Nonrandom
Mating 233 7.1 Migration 234 Computing
Consequences 7.1 An algebraic treatment of migration as an evolutionary process 236 Computing
Consequences 7.2 Selection and migration in Lake Erie water snakes 238 7.2 Genetic Drift 240
Computing Consequences 7.3 The probability that a given allele will be the one that drifts to fixation 248
Computing Consequences 7.4 Effective population
size 251 Computing Consequences 7.5 The rate of evolutionary substitution under genetic drift 256 7.3
Genetic Drift and Molecular Evolution 260 7.4
Nonrandom Mating 275 Computing Consequences
7.6 Genotype frequencies in an inbred population 279
7.5 Conservation Genetics of the Florida Panther 283
Summary 285 • Questions 285 Exploring the Literature 287 • Citations 288 CHAPTER 8 Evolution at Multiple
Loci: Linkage and Sex 291 8.1 Evolution at Two Loci: Linkage Equilibrium and Linkage Disequilibrium 292
Computing Consequences 8.1 The coefficient of linkage disequilibrium 295 Computing Consequences
8.2 Hardy– Weinberg analysis for two loci 296
Computing Consequences 8.3 Sexual reproduction
reduces linkage disequilibrium 301 8.2 Practical
Reasons to Study Linkage Disequilibrium 307
Computing Consequences 8.4 Estimating the age of the GBA–84GG mutation 309 8.3 The Adaptive
Significance of Sex 314 Computing Consequences 8.5
A demographic model of the maintenance of males in the nematode Caenorhabditis elegans 317 Summary
324 • Questions 325 Exploring the Literature 326 •
Citations 327 CHAPTER 9 Evolution at Multiple Loci:
Quantitative Genetics 329 9.1 The Nature of
Quantitative Traits 330 9.2 Identifying Loci That Contribute to Quantitative Traits 334 Computing
Consequences 9.1 Genetic mapping and LOD scores
338 9.3 Measuring Heritable Variation 343 Computing
Consequences 9.2 Additive genetic variation versus dominance genetic variation 345 9.4 Measuring Differences in Survival and Reproductive Success 348 vi Contents Computing Consequences 9.3 The selection gradient and the selection differential 349 9.5 Predicting the Evolutionary Response to Selection
350 9.6 Modes of Selection and the Maintenance of Genetic Variation 356 9.7 The Bell-Curve Fallacy and
Other Misinterpretations of Heritability 360 Summary
365 • Questions 365 Exploring the Literature 367 •
Citations 367 PART 3 ADAPTATION 369 CHAPTER 10
Studying Adaptation: Evolutionary Analysis of Form and Function 369 10.1 All Hypotheses Must Be Tested:
Oxpeckers Reconsidered 370 10.2 Experiments 373 Computing Consequences 10.1 A primer on statistical testing 377 10.3 Observational Studies 378 10.4 The
Comparative Method 382 Computing Consequences
10.2 Calculating phylogenetically independent contrasts 384 10.5 Phenotypic Plasticity 387 10.6
Trade-Offs and Constraints 389 10.7 Selection
Operates on Different Levels 397 10.8 Strategies for Asking Interesting Questions 401 Summary 402 •
Questions 402 Exploring the Literature 404 • Citations
405 CHAPTER 11 Sexual Selection 407 11.1 Sexual
Dimorphism and Sex 408 11.2 Sexual Selection on Males: Competition 417 11.3 Sexual Selection on Males: Female Choice 423 Computing Consequences
11.1 Runaway sexual selection 430 11.4 Sexual
Selection on Females 438 11.5 Sexual Selection in Plants 441 11.6 Sexual Dimorphism in Humans 444
Summary 448 • Questions 448 Exploring the Literature
450 • Citations 451 CHAPTER 12 The Evolution of Social Behavior 455 12.1 Four Kinds of Social Behavior
456 12.2 Kin Selection and Costly Behavior 459
Computing Consequences 12.1 Calculating relatedness as the probability of identity by descent
461 12.3 Multilevel Selection and Cooperation 471
Computing Consequences 12.2 Different perspectives on the same evolutionary process 473 12.4
Cooperation and Conflict 477 12.5 The Evolution of Eusociality 483 Summary 486 • Questions 487
Exploring the Literature 488 • Citations 489 CHAPTER 13 Aging and Other Life-History Characters 491 13.1
Basic Issues in Life-History Analysis 493 13.2 Why Do Organisms Age and Die? 495 Contents vii Computing Consequences 13.1 Late-acting deleterious mutations are weakly selected 501 Computing Consequences 13.2 Alleles conferring early benefits and late costs can be adaptive 504 13.3 How Many Offspring Should an Individual Produce in a Given Year? 513 13.4 How Big Should Each Offspring Be?
517 13.5 Conflicts of Interest between Life Histories
522 13.6 Life Histories in a Broader Evolutionary Context 525 Summary 530 • Questions 530 Exploring the Literature 532 • Citations 532 CHAPTER 14
Evolution and Human Health 535 14.1 Evolving Pathogens: Evasion of the Host’s Immune Response
537 14.2 Evolving Pathogens: Antibiotic Resistance
545 14.3 Evolving Pathogens: Virulence 548 14.4
Tissues as Evolving Populations of Cells 553 14.5
Selection Thinking Applied to Humans 556 14.6
Adaptation and Medical Physiology: Fever 564 14.7
Adaptation and Human Behavior: Parenting 567
Computing Consequences 14.1 Is cultural evolution
Darwinian? 569 Summary 575 • Questions 575
Exploring the Literature 577 • Citations 577 CHAPTER
15 Genome Evolution and the Molecular Basis of Adaptation 581 15.1 Diversity among Genomes 582
15.2 Mobile Genetic Elements 586 15.3 The Evolution of Mutation Rates 591 15.4 Gene Duplication and Gene Families 594 15.5 The Locus of Adaptation in Natural Populations 601 Summary 606 • Questions 606 Exploring the Literature 607 • Citations 608 viii
Contents PART 4 THE HISTORY OF LIFE 609 CHAPTER
16 Mechanisms of Speciation 609 16.1 Species
Concepts 610 16.2 Mechanisms of Isolation 616 16.3
Mechanisms of Divergence 623 16.4 Hybridization and Gene Flow between Species 629 16.5 What Drives
Diversification? 637 Summary 640 • Questions 641
Exploring the Literature 642 • Citations 643 CHAPTER
17 The Origins of Life and Precambrian Evolution 645
17.1 What Was the First Living Thing? 647 17.2 Where
Did the First Living Thing Come From? 655 17.3 What Was the Last Common Ancestor of All Extant
Organisms and What Is the Shape of the Tree of Life?
663 17.4 How Did LUCA’s Descendants Evolve into
Today’s Organisms? 678 Summary 683 • Questions
684 Exploring the Literature 686 • Citations 686
CHAPTER 18 Evolution and the Fossil Record 691 18.1
The Nature of the Fossil Record 692 18.2 Evolution in the Fossil Record 696 Computing Consequences 18.1
Evolutionary trends 706 18.3 Taxonomic and Morphological Diversity over Time 707 18.4 Mass and Background Extinctions 709 18.5 Macroevolution 719
18.6 Fossil and Molecular Divergence Timing 727
Summary 730 • Questions 731 Exploring the Literature
732 • Citations 732 CHAPTER 19 Development and Evolution 735 19.1 The Divorce and Reconciliation of Development and Evolution 736 19.2 Hox Genes and the Birth of Evo-Devo 738 19.3 Post Hox: Evo-Devo 2.0
744 19.4 Hox Redux: Homology or Homoplasy? 763
19.5 The Future of Evo-Devo 764 Summary 765 •
Questions 766 Exploring the Literature 766 • Citations
767 CHAPTER 20 Human Evolution 769 20.1
Relationships among Humans and Extant Apes 770
20.2 The Recent Ancestry of Humans 780 20.3 Origin of the Species Homo sapiens 790 Computing
Consequences 20.1 Using allele frequencies and linkage disequilibrium to date the modern human expansion from Africa 797 20.4 The Evolution of Distinctive Human Traits 802 Summary 807 •
Questions 807 Exploring the Literature 809 • Citations 810 Glossary 815 Credits 822 Index 830
A Case for Evolutionary Thinking: Understanding HIV
Why study evolution? An incentive for Charles Darwin (1859) was that understanding evolution can help us know ourselves. “Light will be thrown,” he wrote, “on the origin of man and his history.” The allure for Theodosius Dobzhansky (1973), an architect of our modern view of evolution, was that evolutionary biology is the conceptual foundation for all of life science. “Nothing in biology makes sense,” he said, “except in the light of evolution.” The motive for some readers may simply be that evolution is a required course. This, too, is a valid inducement. Here we suggest an additional reason to study evolution: The tools and techniques of evolutionary biology offer crucial insights into matters of life and death. To back this claim, we explore the evolution of HIV (human immunodeficiency virus). Infection with HIV causes AIDS (acquired immune deficiency syndrome)—
sometimes, as shown at right, despite triple-drug therapy. Our main objective in Chapter 1 is to show that evolution matters outside of labs and classrooms. However, a deep look at HIV will serve other goals as well. It will illustrate the kinds of questions evolutionary biologists ask, show how an evolutionary perspective can inform research throughout biology, and introduce concepts that we will explore in detail elsewhere in the book. HIV makes a compelling case study because it illustrates public health issues likely to influence the life of every reader. It is an emerging pathogen. It rapidly evolves drug resistance. And, of course, it is deadly. AIDS is among the 10 leading causes of death worldwide (Lopez et al. 2006; WHO 2008). Here are the questions we address: • What is HIV, how does it spread, and how does it cause AIDS? • Why do therapies using just one drug, and sometimes therapies using multiple drugs, work well at first but ultimately fail? • Are human populations evolving as a result of the HIV pandemic? • Where did HIV come from? • Why are untreated HIV infections usually
fatal? While one of these questions contains the word evolution, some of the others may appear unrelated to the subject. But evolutionary biology is devoted to understanding how populations change over time and how new forms of life arise. These are the issues targeted by our queries about HIV and AIDS. In preparation to address them, the first section covers some requisite background. 1.1 The Natural History of the HIV Epidemic AIDS was recognized in 1981, when doctors in the United States reported rare forms of pneumonia and cancer among men who have sex with men (Fauci 2008). The virus responsible, HIV, was identified shortly thereafter (BarréSinoussi et al. 1983; Gallo et al. 1984; Popovic et al. 1984). Nearly always fatal, HIV/AIDS was devastating for those infected. But few physicians or researchers foresaw the magnitude of the epidemic to come (Figure 1.1).
How Does HIV Spread, and How Can It Be Slowed?
A new HIV infection starts when a bodily fluid carries the virus from an infected person directly onto a mucous membrane or into the bloodstream of an uninfected person. HIV travels via semen, vaginal and rectal secretions, blood, and breast milk (Hladik and McElrath 2008). It can move during heterosexual or homosexual sex, oral sex, needle sharing, transfusion with contaminated blood products, other unsafe medical procedures, childbirth, and breastfeeding. HIV has spread by different routes in different regions (Figure 1.3, next page). In sub-Saharan Africa and parts of south and southeast Asia, heterosexual sex has been the most common mode of transmission. In other regions, including Europe and North America, male–male sex and needle sharing among injection drug users have predominated. Certain activities are particularly risky. For example, data on men who have sex with men in Victoria, Australia, show that having receptive anal intercourse with casual partners without the protection of a condom is a dangerous behavior. Individuals who report practicing it are nearly 60 times as likely to be infected with HIV as
individuals who do not report practicing it (Read et al. 2007).
Clinical studies in which volunteers are randomly assigned to treatment versus control groups have identified medical interventions that reduce the rate of HIV transmission. Use of antiviral drugs, for example, lowers the risk that infected mothers will pass the virus to their infants by about 40% (Suksomboon et al. 2007). Antivirals are similarly effective in reducing transmission among men who have sex with men (Grant et al. 2010). Circumcision reduces the risk that men will contract HIV by about half (Bailey et al. 2007; Gray et al. 2007). Antiviral vaginal gels are comparably beneficial for women (Abdool Karim et al. 2010). The value of encouraging people to change their behavior is less clear. Behavioral change undoubtedly has the potential to curtail transmission. Consistent use of condoms, for example, may reduce the risk of contracting HIV by 80% or more (Pinkerton and Abramson 1997; Weller and Davis 2002). And there are apparent success stories. In Uganda, for instance, a campaign discouraging casual sex and
promoting condom use and voluntary HIV testing is thought to have substantially reduced the local AIDS epidemic (Slutkin et al. 2006; but see Oster 2009). On the other hand, the results of randomized controlled trials have been somewhat disappointing. A study of over 4,000 HIV-negative men who have sex with men in the United States offered extensive one-on-one counseling to members of the experimental group and conventional counseling to the control group (Koblin et al. 2004). As hoped, the experimental subjects engaged in fewer risky sexual behaviors than the controls. However, the rates at which the experimentals versus the controls contracted HIV were not statistically distinguishable. There is clearly no room for complacency. The graph in Figure 1.4 tracks the number of new infections each year among men who have sex with men in the United States. After falling from the mid 1980s to the early 1990s, the annual number of new infections has since been rising steadily. The same thing seems to be happening elsewhere (Hamers and Downs 2004; Giuliani et al. 2005). Results of surveys suggest that the introduction of effective long-term drug therapies, which for some individuals has at least temporarily transformed HIV into a
manageable chronic illness, has also prompted an increase in risky sexual behavior (Crepaz, Hart, and Marks 2004; Kalichman et al. 2007). What Is HIV?
Like all viruses, HIV is an intracellular parasite incapable of reproducing on its own. HIV invades specific types of cells in the human immune system. The virus hijacks the enzymatic machinery, chemical materials, and energy of the host cells to make copies of itself, killing the host cells in the process. 4
Part 1 Introduction 80 40 20 0 60 76 84 92 00 New infections (1,000s) Year Figure 1.4 New HIV infections among men who have sex with men in the United States From Hall et al. (2008). (b) Estimated new infections, by likely mode of transmission: (a) Estimated new infections, by likely mode of transmission: Cambodia 2002 Honduras 2002
Kenya 1998 Russia 2002 Indonesia 2002 U.S. 2006
Canada 2005 U.K. 2007 Male–male sex (MMS)
MMS & IDU Injection drug use (IDU) Heterosexual sex Other Heterosexual sex with a partner at high risk Casual heterosexual sex Male–male sex Sex work Injection drug use Figure 1.3 HIV’s main routes of transmission in various regions (a) From Pisani et al. (2003). (b) From Hall et al. (2008), Public Health Agency of Canada (2006), Health Protection Agency
(2008). The authors of the reports on Canada and the United Kingdom note that many of the individuals who contracted HIV through heterosexual sex likely did so in sub-Saharan Africa. See also UNAIDS (2008). Figure 1.5 outlines HIV’s life cycle in more detail (Nielsen et al. 2005; GanserPornillos et al. 2008). The life cycle includes an extracellular phase and an intracellular phase. During the extracellular, or infectious phase, the virus moves from one host cell to another and can be transmitted from host to host. The extracellular form of a virus is called a virion or virus particle. During the intracellular, or replication phase, the virus replicates. HIV initiates its replication phase by latching onto two proteins on the surface of a host cell. After adhering first to CD4, HIV attaches to a second protein, called a coreceptor. This leads to fusion of the virion’s envelope with the host’s cell membrane and spills the contents of the virion into the cell. The contents include the virus’s genome (two copies of a single-stranded RNA molecule) and two viral enzymes: reverse transcriptase, which transcribes the virus’s RNA genome into DNA; and integrase, which splices this DNA genome into the host cell’s genome. Once HIV’s genome has
infiltrated the host cell’s DNA, the host cell’s RNA polymerase transcribes the viral genome into viral mRNA. The host cell’s ribosomes synthesize viral proteins. New virions assemble at the host cell’s membrane, then bud off into the bloodstream or other bodily fluid. Inside the new virions, HIV’s protease enzyme cleaves precursors of various viral proteins into functional forms, allowing the virions to mature. The new virions are now ready to invade new cells in the same host or to move to a new host. A notable feature of HIV’s life cycle is that the virus uses the host cell’s own enzymatic machinery its polymerases, ribosomes, and tRNAs, and so on—in
Chapter 1 A Case for Evolutionary Thinking: Understanding HIV 5 HIV proteins 7 Coreceptor Translation Host cell 6 Transcription 8 New virion assembly Integrase Protease RNA genome (2 copies) Reverse transcriptase gp120 (surface protein) 1 HIV virion gp41 (anchor protein for gp120) HIV RNA HIV DNA 5 DNA splicing Host-cell nucleus
Host-cell DNA HIV mRNA HIV reverse transcriptase HIV integrase 9 Budding Mature virus Host-cell membrane 4 DNA synthesis 2 Binding 3 Fusion 10 maturation CD4 Protease Figure 1.5 The life cycle of HIV (1, upper left) HIV’s extracellular form, known as
a virion, encounters a host cell (usually a helper T cell). (2) HIV’s gp120 surface protein binds first to CD4, then to a coreceptor (usually CCR5; sometimes CXCR4) on the surface of the host cell. (3) The HIV virion fuses with the host cell; HIV’s RNA genome and enzymes enter the host cell’s cytoplasm. (4) HIV’s reverse transcriptase enzyme synthesizes HIV DNA from HIV’s RNA template. (5) HIV’s integrase enzyme splices HIV’s DNA genome into the host cell’s genome. (6) HIV’s DNA genome is transcribed into HIV mRNA by the host cell’s RNA polymerase. (7) HIV’s mRNA is translated into HIV precursor proteins by host cell’s ribosomes. (8) A new generation of virions assembles at the membrane of the host cell. (9) New virions bud from the host cell’s membrane. (10) HIV’s protease enzyme cleaves precursors into mature viral proteins, allowing the new virions to mature. HIV is a parasite that afflicts cells of the human immune system. HIV virions enter host cells by binding to proteins on their surface, then use the host cells’ own machinery to make new virions. almost every step. This is why HIV, and viral disease in general, is so difficult to treat. It is a challenge to find drugs that interrupt the viral life cycle without also disrupting
the host cell’s enzymatic functions and thus causing debilitating side effects. Effective antiviral therapies usually target enzymes specific to the virus, such as reverse transcriptase and integrase. How Does the Immune System React to HIV? A patient’s immune system mobilizes to fight HIV the same way it moves to combat other viral invaders. Key aspects of the immune response appear in Figure 1.6. Sentinels called dendritic cells patrol vulnerable tissues, such as the lining of the digestive and reproductive tracts (Banchereau and Steinman 1998). When a dendritic cell captures a virus, it travels to a lymph node or other lymphoid tissue and presents bits of the virus’s proteins to specialized white blood cells called naive helper T cells (Sprent and Surh 2002). Naive helper T cells carry highly variable proteins called T-cell receptors. When a dendritic cell presents a helper T cell with a bit of viral protein that binds to the T cell’s receptor, the helper T cell activates. It grows and divides, producing daughter cells called effector helper T cells. Effector helper T cells help coordinate the immune response. Effector helper T cells issue commands, in the form of molecules called cytokines, that help mobilize a variety of immune cells to join the fight. They induce B cells to mature
into plasma cells, which produce antibodies that bind invading virions and mark them for elimination (McHeyzer-Williams et al. 2000). They activate killer T cells, which destroy infected host cells (Williams and Bevan 2007). And they recruit macrophages (not shown), which destroy virus particles or kill infected cells (Seid et al. 1986; Abbas et al. 1996).
Most effector helper T cells die within a few weeks. However, a few survive and become memory helper T cells (Harrington et al. 2008). If the same pathogen invades again, the memory cells produce a new population of effector helper T cells. How Does HIV Cause AIDS? As we noted earlier, HIV invades host cells by first latching onto two proteins on the host cell’s surface. The first of these is CD4; the second is a called a coreceptor. Different strains of HIV exploit different coreceptors, but most strains responsible for new infections use a protein called CCR5. Cells that carry both CD4 and CCR5 on their membranes, and are thus vulner6 Part 1
Introduction Virus (+) (+) cytokines (a) Dendritic cells capture the virus and present bits of its proteins to naive helper T cells. Once activated, these naive cells divide to produce effector helper T cells.
Dendritic cell Naive helper T cell Effector helper T
cell Antibodies Plasma cells B cell Effector killer T cells T-cell receptor Effector helper T cells also help activate killer T cells, which destroy host cells infected with the virus. (b) Effector helper T cells stimulate B cells displaying the same bits of viral protein to mature into plasma cells, which make antibodies that bind and in some cases inactivate the virus. Effector helper T cell Effector helper T cells Effector helper T cells Memory helper T cell
Naive killer T cell (c) Most effector T cells are short lived, but a few become long-lived memory helper T cells. Figure 1.6 How the immune system fights a viral infection After NIAID (2003) and Watkins (2008). Chapter 1 A Case for Evolutionary Thinking: Understanding HIV 7 able to HIV, include macrophages, effector helper T cells, and memory helper T cells (Figure 1.7). The progress of an HIV infection can be monitored by periodically measuring the concentration of HIV virions in the patient’s bloodstream and the concentration of CD4 T cells in the patient’s bloodstream and in the lymphoid (immune system) tissues associated with the mucous membranes of the gut. A typical untreated infection progresses through three phases. In the acute phase, HIV virions enter the host’s body and
replicate explosively. The concentration of virions in the blood climbs steeply (Figure 1.8). The concentrations of CD4 T cells plummet—especially in the lymphoid tissues of the gut. During this time, the host may show general symptoms of a viral infection. The acute phase ends when viral replication slows and the concentration of virions in the bloodstream drops. The host’s CD4 T-cell counts recover somewhat. During the chronic phase, the patient usually has few symptoms. HIV continues to replicate, however. The concentration of virions in the blood may stabilize for a while, but eventually rises again. Concentrations of CD4 T cells fall. The AIDS phase begins when the concentration of CD4 T cells in the blood drops below 200 cells per cubic millimeter. By now the patient’s immune system has begun to collapse and can no longer fend off a variety of opportunistic viruses, bacteria, and fungi that rarely cause problems for people with robust immune systems. Without effective anti-HIV drug therapy, a patient diagnosed with AIDS can expect to live less than three years (Schneider et al. 2005).
The mechanisms by which an HIV infection depletes the patient’s CD4 T cells and undermines the patient’s immune system are complex. Despite a
quarter century of research, they remain incompletely understood (Pandrea et al. 2008; Douek et al. 2009; Silvestri 2009). The simple infection and destruction of host CD4 T cells may explain their precipitous loss during the acute phase of infection. But the immune system has an impressive capacity to regenerate these cells. Furthermore, during the chronic phase no more than one CD4 T cell in a hundred is directly infected. There must be more to the story.
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