Exam 2 Lectures - Bio Evo

Discussion on Genome Size

• Trends have been observed in genome sizes across different organisms.✅

  • There is a noticeable pattern in small organisms like viruses and bacteria, where smaller genomes correspond to fewer coding regions.

  • In contrast, multicellular organisms exhibit an increase in genome size, yet the amount of coding DNA tends to plateau. This suggests the presence of a significant quantity of non-coding DNA, which may play crucial roles in genetic regulation and function.

Genome Structures Across Organisms

• As an example, the SARS-CoV genome (note: not related to COVID) is characterized by its single-stranded RNA, approximately 30,000 base pairs long, coding for four proteins crucial for its life cycle.

• Differences exist in the genome structures of various viruses, such as influenza and hepatitis viruses, highlighting the diversity of viral genomes.

Viral Genomes

• Flu Virus:

  • Composed of single-stranded RNA, divided into eight segments of chromosomes that facilitate genetic reassortment during co-infection.

  • Encodes multiple proteins critical for viral assembly and replication, which are targeted by antiviral drugs.

• Hepatitis Virus:

  • Features double-stranded DNA and encodes five proteins with a unique coding structure, including overlapping reading frames that maximize the use of genetic material.

  • This configuration poses challenges for treatment due to the complexity of the virus’s replication cycle.

Bacterial Genomes

• Structure:

  • Bacterial genomes are primarily composed of circular DNA molecules. They are generally larger than viral genomes but smaller than those found in eukaryotes.

  • These genomes consist mostly of coding sequences, though they also contain pseudogenes and plasmids, which can recombine with the main genome, allowing bacteria to acquire new traits.

• Horizontal Gene Transfer: Bacterial genomes can change through several mechanisms:

  • Transformation: Uptake of free DNA from the environment, leading to genetic variation.

  • Transduction: Virus-mediated transfer of DNA between bacteria, contributing to genetic diversity.

  • Conjugation: Direct transfer of genetic material between bacteria, often involving plasmids that confer advantageous traits, such as antibiotic resistance.

Eukaryotic Genomes

• Structure:

  • Eukaryotic genomes are organized within a nucleus and consist of multiple linear chromosomes, which allows for complex regulation of gene expression.

  • A large proportion (approximately 98%) of eukaryotic genomes is non-coding DNA, including regulatory elements such as introns and transposable elements that contribute to gene regulation and evolution.

• Gene Conservation:

  • Comparative analysis of human and mouse genomes reveals significant structural similarities, underscoring the conserved nature of many essential genes across species.

Recombination Rate and Genome Size

• The recombination rate during meiosis exhibits an inverse relationship with genome size: larger genomes tend to show lower recombination rates, which can impact evolutionary dynamics.

  • larger genomes tend to evolve mechanisms to limit excessive recombination to preserve stability.

Genetic Code and Codons

• Codon Redundancy: There is redundancy in the genetic code, where multiple codons can code for the same amino acid, influencing protein synthesis efficiency.

• Codon preference exists, with specific codons being favored for amino acids like leucine due to higher tRNA availability, which streamlines the translation process.

  • Because the tRNA molecules that recognize those preferred codons are more abundant, making translation faster and more efficient.

• Mutations are frequently observed (for instance, transitions like G to A and C to T), which can have significant implications for genetic variation and adaptation.

• Factors influencing codon usage include cellular efficiency and the relative abundance of tRNA species.

GC Content

• Definition: GC content refers to the frequency of guanine and cytosine bases in a genome, serving as a crucial indicator of genomic stability.

• Organisms with high GC content, particularly certain bacteria, are often associated with environments of higher stability, such as extreme temperatures, due to the increased thermal stability offered by GC base pairs.

Key Takeaways

• A comprehensive understanding of genome structure is critical for examining how genes and genomes may change or be modified over time.

• There is a necessity to focus not only on the structure but also on the functional implications of different genome types across various organisms, including their evolutionary adaptations and interactions with environmental factors.

CH16: Evolution of Sex

Overview of Sexual and Asexual Reproduction

Sexual reproduction is a critical part of the life cycle of many organisms, despite being a smaller component in terms of the number of times it occurs. Life cycles typically alternate between diploid (with two sets of chromosomes) and haploid (with one set of chromosomes) stages, which is essential for genetic diversity.

Life Cycle Structure

Visualize a circular representation of life cycles with a clear demarcation between haploid and diploid stages. Meiosis, which is a specialized type of cell division, leads to the haploid stage in the life cycle and is crucial for the production of gametes (sperm and eggs). This stage allows for genetic recombination and variation among offspring.

Asexual Reproduction Modes

There are different modes of asexual reproduction, including Aplomixis and Automixis.

• Aplomixis: This mode of asexual reproduction allows for the production of offspring without any fertilization taking place. Offspring are typically clones of the parent, which means there is no genetic variation. This can be advantageous in stable environments where the parent's genetic traits are well-suited for survival.

• Automixis: Often referred to as "self-mixing," this involves the fusion of proto egg cells within the female reproductive tract. While it can create genetic diversity, it tends to be less significant than the variation produced during sexual reproduction.

Impact of Reproduction Methods

• Asexual Populations: In populations that reproduce asexually, different genotypes can reproduce to create clones. These populations do not typically engage with other clones, resulting in limited genetic diversity, which can lead to vulnerability to diseases and environmental changes.

• Sexually Reproducing Populations: These populations benefit from genetic exchange, leading to larger and more diverse populations. This diversity enhances the ability of the group to adapt to changing environments and improves their chances of survival and evolution over generations.

Effects of Parasites in Populations

As the frequency of parasites increases in a given ecosystem, the populations of their hosts (e.g., snails) may experience significant declines. This dynamic has critical implications for biodiversity and ecological stability.

Population Dynamics

Population dynamics can be observed through experiments involving algal food sources that diverse groups of organisms consume.

• Experiment Example:

  • Chryptomonis: This type of algae is recognized as a high-quality food source, promoting the health and growth of the consuming population.

  • Semidesmis: In contrast, this lower-quality algae can adversely affect the health and well-being of the organisms that rely on it as a food source, demonstrating how different food quality can influence population dynamics.

Sexual Selection

Sexual Selection Overview

• Concept coined by Charles Darwin, focusing on the differences between sexes in terms of traits and selection.

• Unlike natural selection, which is influenced by the environment, sexual selection involves active choices made by individuals of one sex (often females) regarding traits in the other sex.

Gamete Size and Isogamy vs. Anisogamy

Gamete Types

• Isogamy: Organisms with gametes of the same size (e.g., some marine invertebrates, algae).

• Anisogamy: Most animals exhibit different sized gametes, typically large eggs (females) and small sperm (males).

Evolution of Gamete Size

• Larger gametes increase survival chances but reduce mobility.

• This leads to a disruptive selection, resulting in two gamete strategies: larger, non-motile eggs vs. smaller, motile sperm.

Investment and Reproductive Strategies

• Males generally produce numerous, less costly sperm; females produce fewer, more costly eggs.

• This difference leads to a varying level of choosiness between the sexes:

  • Males: Often less selective due to the abundance of sperm.

  • Females: Tend to be choosy due to the higher reproductive investment.

Sexual Dimorphism

• Males frequently exhibit traits such as bright colors and larger body sizes compared to females.

• Traits often serve as signals of fitness and health, crucial for mating success.

Female Choice

Selection Mechanisms

• Females make selective choices based on traits with perceived advantages:

  • Direct Benefits: Some traits offer clear survival advantages (e.g., larger males reduce predation risk for females).

  • Good Genes Hypothesis: Traits may indicate overall fitness and genetic quality (e.g., peacock tails).

• The Handicap Principle suggests that costly traits signal better genes and resources, as only healthy individuals can afford to develop such traits.

Human Examples of Sexual Selection

Fluctuating Asymmetry

• Fluctuating asymmetry (FA) refers to deviations from perfect symmetry in bilateral organisms, potentially linked to fitness and health.

• Studies indicate women prefer symmetrical men, and their preference varies according to their menstrual cycle and hormonal state.

Male Choice Based on Female Traits

• Male choice can be influenced by female signals; for example, men might respond differently based on female fertility.

Case Studies in Animal Behavior

Howler Monkeys

• Males with deeper, lower-frequency howls preferred by females; this requires larger hyoid bones, which trade-off with sperm production.

Seahorses and Role Reversal

• In species like seahorses, males invest more in offspring care, leading to a reversal in choosiness where males become more selective due to higher risks associated with mate choice.

  • Since males are the ones carrying and protecting the developing offspring, choosing a low-quality mate could mean wasting valuable reproductive resources on weaker offspring.

Fisherian Selection

• Named after Ronald Fisher, this involves a runaway process in trait exaggeration, where females prefer increasingly extreme male traits, regardless of their survival costs.

  • females prefer an attractive trait that is not specifically beneficial, and the gene for this gets passed on (peacock tails)

Conclusion

• Sexual selection encompasses complex interactions between traits and reproductive strategies, influenced by environmental factors and individual choices, leading to diverse evolutionary outcomes across species.

Sexual Selection P2

Sexual Selection Overview

• Definition: Sexual selection is a specialized case of natural selection where individuals in one sex select traits in the other sex.

• Mechanism: Unlike natural selection which is influenced by the environment, sexual selection is driven by mate choice.

• Genetic Basis: Adaptation may occur if selected traits have a genetic basis, leading to potential evolutionary changes.

Differences Between Males and Females

• Males and females have contrasting strategies in reproduction due to differences in gametes:

  • Males typically produce many small gametes (sperm).

  • Females produce fewer, larger gametes (eggs).

• Due to these differences, there are distinct interests in mating and reproductive success.

Female Choice and Good Genes Hypothesis

• Female Choice: Females often select mates based on traits that indicate good genes or health.

• Good Genes Hypothesis: The hypothesis suggests that certain traits are reliable indicators of a male's fitness or ability to provide offspring survival.

  • Example: The size and brightness of a peacock's tail can indicate genetic fitness, as maintaining such traits entails higher survival risks.

• Fluctuating Asymmetry: The concept refers to variations from perfect bilateral symmetry, which may signal health and genetic quality.

• Research Ethics: Importance of ethical practices in studies with human subjects and animals, emphasizing transparency and participant protection.

Example Studies on Sexual Selection

• Howler Monkeys: Females select males based on vocalization frequencies correlated with anatomical features like hyoid bone size.

• Role Reversal in Seahorses and Pipefish: Males invest in offspring care, choosing larger females for breeding based on their potential for more eggs.

Fisherian Runaway Selection

• Definition: A process where female preferences for specific male traits lead to exaggerated male characteristics over generations.

• Characteristics may evolve even if they do not directly benefit survival, creating a feedback loop of trait exaggeration.

  • Example: Brightly colored sticklebacks use coloration to attract mates and signal health, despite attracting potential predators.

Intrasexual Selection and Sexual Conflict

• Intrasexual Selection: Competition among males for access to females; males often exhibit traits like large size or armaments (e.g., horns in deer).

• Sexual Conflict: Occurs when the reproductive interests of males and females differ, leading to strategies like polygyny or polyandry.

  • Males benefit from having multiple female mates, while females may suffer reduced success if the male divides attention.

Mating Systems

• Monogamy: One male pairs with one female.

• Polygyny: One male mates with multiple females; this occurs more favorably in environments with abundant resources.

• Polyandry: One female mates with multiple males; less common but offers strategic benefits in certain ecological contexts.

• Polygynandry: Multiple males and multiple females form breeding groups, leading to complex mating dynamics.

Practical Example: Red-winged Blackbirds

• Mating Behavior: Males establish territories and attract females through vocalizations and displays.

• Extra-Pair Fertilization: Females may engage in copulations outside their primary pair bond, allowing genetic variation.

• Environmental Impact: The success of mating strategies is highly dependent on habitat quality and resource availability.

  • In good environments, polygenic systems can thrive without significantly harming reproductive success for females.

Evolution in Medicine

Importance of Evolution in Medicine

The significance of evolutionary biology in medicine has grown exponentially, particularly in the context of contemporary medical education. Understanding evolution provides a framework for comprehending how organisms function and interact with their environments, which, in turn, has profound implications for health and disease. Modern medical curricula increasingly incorporate evolutionary concepts to better equip future medical professionals with the knowledge needed to understand the complexities of human health.

Key Points of Today's Lecture

Evolutionary Implications of Diseases

• Contributions of Evolutionary Biology: Evolutionary biology offers valuable insights into the underlying mechanisms of diseases, symptoms, and health outcomes. By exploring how evolutionary pressures shape human physiology, we gain a deeper understanding of various medical conditions.

• Adaptive Responses: An example discussed during the lecture was fever. Fevers are not merely symptoms but adaptive physiological responses that serve to enhance the immune response against infections. They are evolutionary adaptations that help individuals survive infections, indicating that our bodily responses are shaped by natural selection.

• Understanding Aging: Aging is framed not only as a chronological process but also through the lens of evolutionary constraints. Various species exhibit different aging processes influenced by their ecological niche and evolutionary history, leading to a broader understanding of senescence.

Developmental Constraints and Costs

• Compromises in Evolution: Evolution often results in trade-offs due to genetic and anatomical limitations within species. This emphasizes that evolutionary development is not linear and must navigate complexity.

• Host-Parasite Interactions: The dynamics of evolution include host-parasite interactions, which are critical for understanding disease emergence and transmission. Evolutionary pressures exerted by pathogens shape host defenses, leading to an ongoing evolutionary arms race that influences both health and disease.

The Nature of Evolution

• Evolution as an Optimizing Process: While evolution fosters refinement of traits, it does not create perfect organisms. Instead, it optimizes traits for survival based on varying environmental contexts, providing a foundation for understanding health-related issues faced by humans.

• Arms Race with Pathogens: The continued co-evolution of humans and pathogens exemplifies a constant battle for survival, where pathogens adapt quickly to host defenses. This lag in adaptation on the part of human hosts often results in increased susceptibility to new diseases, underscoring the importance of evolutionary understanding in modern medicine.

Mechanisms Behind Illness

• Compromises between Traits: Illness can arise from evolutionary compromises where traits that promote reproductive success may detract from longevity or health. For instance, high reproductive output may require significant metabolic investment, potentially leading to conditions such as chronic diseases in later life.

  • traits or behaviors that increase reproductive success may also come with negative side effects on an individual’s health or lifespan

• Metabolic Costs: The costs associated with sustaining high metabolic rates can also influence overall health and lifespan, reflecting the delicate balance inherent to evolutionary adaptations.

Trade-offs in Evolutionary Strategies

• Reproductive Success vs. Longevity: Characteristics that favor reproductive success may not align with modern human health needs, presenting a challenge for medical practitioners aiming to treat diseases effectively in a rapidly changing world.

Example Case: Fever

• Fever as an Evolved Trait: Fever is a sophisticated physiological mechanism evolved to combat pathogens, observed across various taxa such as warm-blooded mammals and some cold-blooded animals. This demonstrates a common evolutionary strategy aimed at enhancing survival against infections.

• Behavioral Fever: In ectothermic creatures, such as lizards, behavioral fever illustrates how some animals increase their body temperature by seeking warmth when infected, showcasing a different dimension of evolutionary adaptation to combat disease.

• Implications for Fever Management: Discussions around fever management highlighted the importance of recognizing fevers' roles in healing. Some medical professionals caution against immediately administering antipyretics, as fevers may help the body fight infections—though dangerously high fevers necessitate careful intervention to avoid harm.

Aging and Senescence

• Understanding Senescence: Aging is described as a physiological process with significant variability that can occur independent of chronological age. The factors contributing to aging processes differ widely among species.

• Theories of Aging:

  • "Wear and Tear" Hypothesis: This perspective gives insight into how genetic variation can affect lifespan and longevity. Persistent environmental challenges exert selective pressures, leading to adaptations and variations in aging across populations.

Conclusion

In summary, the integration of evolutionary principles into medical practice enhances our understanding of health, disease, and aging. A comprehensive grasp of these processes is crucial for preparing future healthcare professionals to address challenges in medicine effectively, leading to improved patient outcomes and advancements in medical practices. Understanding the evolutionary context of diseases and the nature of human biology can significantly enhance the way medical difficulties are approached and treated in practice.

Sexual Selection

• Reproductive Success:
  - Males: Reproductive success increases with access to multiple females, whereas sharing among males may still occur and can lead to increased genetic diversity, as males who mate with various partners could enhance the overall gene pool.

  • Females: Female reproductive success is primarily linked to exclusive access to a male, as it increases the likelihood of successful fertilization. In some scenarios, sharing may be advantageous, allowing females to secure better genetic traits or resources by mating with genetically superior males, a phenomenon known as polyandry.

Survivorship Curves

• Definition:
  - Represents the proportion of individuals from a cohort that survive across different life stages over time. These curves serve as important visual tools in understanding mortality rates and life expectancy within populations.

  • Tracks survival from an initial explicit number of individuals, often categorized into three types: Type I (high survival rates in early and middle stages, dropping dramatically in old age), Type II (constant mortality rates regardless of age), and Type III (low survival rates early in life with a higher survival rate for those who make it past a critical age).

Early vs. Late-Acting Mutations

• Late-Acting Mutations:
  - These mutations tend to have a negligible impact since there are fewer individuals alive to express these mutations, resulting in lower visibility in the population's phenotype across generations.

• Early-Acting Mutations:
  - Early-acting mutations have a significant impact as they are expressed while a greater number of individuals are alive, allowing these mutations to be passed on and become more common within the population.

Mutation Accumulation Hypothesis

• Originally conceptualized before the mechanism of DNA was fully understood, this hypothesis suggests that late-onset mutations are less purged by natural selection compared to early-onset mutations. This is integral in understanding genetic load and the potential for populations to accumulate deleterious mutations over time.

Population Studies: Possums

• A comparison of island vs. mainland populations of possums has shown notable differences in longevity that are unrelated to predation pressures. Findings indicate evidence of physiological changes in bone structure among the populations. Such changes suggest that mainland possums may experience a greater rate of senescence (aging), possibly due to environmental stresses or competition that differ significantly from island populations.

Introduction to Viruses and Viral Evolution

• Understanding viruses is crucial, particularly in light of recent outbreaks like COVID-19 and measles, which underscore the importance of studying viral transmission, mutation, and impact on public health. Viruses are generally categorized into lytic and lysogenic viruses based on their life cycles and methods of infection.

Virus Characteristics

• Definition:

  • Viruses are often debated as living entities. They lack metabolic processes and replication capabilities outside a host cell, yet they can evolve and reproduce by hijacking the cellular machinery of host organisms.

• Life Cycles:

  • Lytic Viruses: Infect host cells, rapidly replicate their genetic material, produce copies of the virus, and ultimately destroy the host cell in the process. Examples include HIV and SARS-CoV-2 (the virus causing COVID-19).

  • Lysogenic Viruses: Incorporate their genetic material into the host cell's DNA, allowing them to remain dormant for extended periods before triggering a lytic cycle. Herpes simplex virus is a notable example of this type.

Types of Viruses

• Coronaviruses

  • Cause a range of illnesses, from mild conditions like the common cold to severe diseases such as Middle East Respiratory Syndrome (MERS).

  • Mutation Rates: Coronaviruses typically exhibit moderate to high mutation rates, leading to the emergence of new variant strains that can elude the immune response or vaccination.

Influential Strains

• HIV: Displays high evolutionary rates, resulting in significant genetic diversity that contributes to its complexity and challenges in treatment.

• Flu Viruses: They manifest various subtypes that differ in severity, with zoonotic transmission (transfer from animals to humans) playing a critical role in their evolution and adaptability.

Zoonotic Diseases

• Definition:
  - Zoonotic diseases are those that can jump from animals to humans, examples include the flu and HIV.

  • Human behaviors, such as hunting wildlife and encroaching on animal habitats, alongside ecological changes, are significant factors contributing to zoonotic spillover. Recent examples illustrate this, including the resurgence of measles in Texas and historical insights into past epidemics like the Spanish flu, which also had zoonotic origins.

Coevolution of Hosts and Viruses

• The process of coevolution between hosts (such as humans) and viruses is critical as they impact one another's survival over time.

• Arms Race Metaphor: This phrase aptly describes the ongoing evolutionary battle where host defenses evolve in response to viral adaptations, and vice versa, leading to constant changes in virulence and infectivity.

Viral Evolution Insights

• The rapid reproduction of viruses leads to high mutation rates, enabling them to adapt swiftly to changing environments and immune responses. Different strains may evolve with varying mortality rates and transmissibility, as evidenced in the COVID-19 pandemic.

  • Variants like Delta and Omicron have demonstrated notable differences in transmissibility and impacts on public health responses and outcomes, necessitating ongoing monitoring and research.

Emerging Diseases & Perspectives on Virulence

• Contrary to popular belief, not all viruses evolve toward lower lethality; this idea is a myth as some viruses can maintain or even increase their virulence based on their ecological context.

• Examples:
  - Smallpox & Polio: Historically, these viruses were associated with significant mortality and did not demonstrate significant shifts toward lower lethality over time.

  • Measles: The current outbreak illustrates serious health threats, even in the presence of existing vaccines, highlighting the need for ongoing vigilance and public health interventions.

Conclusion

• Public awareness of viral evolution and its implications is crucial for effective public health strategies.

• Understanding the dynamics of coevolution aids in comprehending the emergence and persistence of diseases within populations and encourages proactive measures for prevention and control.

Overview of Measles and Vaccination Rates

Measles Eradication

Measles was effectively eliminated in the U.S. through comprehensive vaccination campaigns until recent years, when a notable decline in vaccination rates has led to a troubling resurgence of the disease. This decline is attributed to various factors, including vaccine hesitancy and the spread of misinformation about vaccine safety.

Role of CDC

Despite the CDC's typical intervention strategies, it has faced significant challenges in monitoring and testing due to substantial funding cuts at the federal and state levels. These cuts have critically impaired the agency’s ability to respond promptly to outbreaks and maintain public health standards.

Vaccination Statistics

Texas requires childhood vaccinations, but there are exemptions available for parents who choose to opt out, citing personal or religious beliefs. A publicly accessible spreadsheet on the state’s website details vaccination rates for various diseases in schools, revealing concerning trends in vaccine uptake. Recently, cases of mumps and rubella have been reported, underscoring the interconnected risks that arise from lower vaccination rates against vaccine-preventable diseases.

Importance of Vaccination Rates

Vaccination Thresholds

To effectively mitigate measles outbreaks, a vaccination rate of approximately 95% is necessary. However, some local schools report alarmingly low vaccination levels, such as:

• Academy and Broadway: 72%

• Longview Christian School: 62%This significant disparity in immunization levels raises the risk of outbreaks as measles spreads rapidly in unvaccinated populations.

Consequences of Lower Rates

Lower vaccination rates increase the likelihood of virus spread, as measles is one of the most contagious viruses known. Transmission can occur through airborne particles that can remain viable in the environment for hours, posing risks even in public spaces.

Evolution of Viruses

Virus Evolution

Viruses like measles, rabies, and HIV are subject to evolution, affecting their transmission and virulence. Rabies remains highly lethal, with very few documented survivors, highlighting the critical need for diligent vaccination, especially in potential exposure situations.

HIV Studies

Ongoing research into HIV suggests that less lethal strains may be evolving, which could significantly impact vaccine development strategies and public health response initiatives.

Booster Vaccinations

It is essential to note that not all vaccines confer lifelong immunity; many require booster doses to maintain their effectiveness against disease. This requires public awareness and action to keep vaccination rates high.

Herd Immunity Concept

Definition of Herd Immunity

Herd immunity is achieved when a sufficient portion of the population is immune to a disease, thereby restricting its spread. For measles, herd immunity relies on about 95% of the population being vaccinated.

Challenges in Achieving Herd Immunity

Maintaining high vaccination rates is a continual challenge, particularly as new variants of viruses emerge. This interplay between vaccines, immunity, and pathogen evolution complicates public health strategies.

Red Queen Hypothesis in Viral Evolution

Concept Introduction

The Red Queen Hypothesis describes the constant evolutionary arms race between hosts and pathogens, emphasizing the need for adaptation in both to survive.

Application to Vaccines

Immunity resulting from vaccination can drive viral evolution, leading to the emergence of new strains that can evade existing immune responses. This cyclical nature of viral mutation necessitates ongoing updates to vaccines to ensure their effectiveness.

Cactus-Shaped Phylogeny

The cactus-shaped phylogeny model demonstrates how viruses evolve through interactions with host immune defenses, showcasing the dynamic nature of viral evolution and response to immunization efforts. Vaccines like those for measles effectively limit the virus's ability to mutate and thrive.

Additional Notes on Virus Evolution Trends

Flu and COVID Vaccination Strategies

Vaccination strategies for flu and COVID-19 continue to adapt as new circulating variants are monitored closely. There are ongoing discussions surrounding upcoming vaccine designs and potential delays in CDC meetings to keep pace with changing public health realities.

HIV Phylogeny

The diverse evolutionary patterns observed in individual HIV infections pose significant challenges for treatment efforts and developing effective immunity.