Topic 1- Intro-Overview

Question 1

Linnaeus 1758

Answer 1

hierarchical classification of organisms; (Systema Naturae book by Linnaeus)

Question 2

Jean-Baptiste Lamarck early 1800s

Answer 2

proposed the concept of evolution

Question 3

Darwin & Wallace 1858-1859:

Answer 3

natural selection and evolution (Origin of Species 1859 by Darwin)
-Darwin published On the Origin of Species in 1859 which describes how natural selection provides a mechanistic explanation of how species change over time and how new species evolve.

Question 4

Mendel 1866:

Answer 4

inheritance in peas (“Experiments in plant hybridization”. Journal Royal Horticultural Society 26: 1–32, 1866)

Question 5

Ronald A. Fisher, Julian Huxley and others 1936-1947:

Answer 5

modern synthesis (Evolution: The Modern Synthesis, 1942 by Julian Huxley)

Question 6

Watson & Crick 1953

Answer 6

double helix of DNA (Nature 171, 738-740, 1953) enabled evolutionary processes to be understood at the biochemical level

Question 7

Linnaeus classification system

of organisms in 1758

Answer 7

Carl Linnaeus in 1758, published his Systema Naturae book describing thousands of plants, fungi, and animals in a hierarchical classification system of taxonomy with species, genera, families, orders, classes, phyla, & kingdoms.
• Binomial system of species names e.g., Homo sapiens
• His underlying definition of a species was the ability of individuals within the species to interbreed and produce viable offspring.
• However, Linnaeus thought that species were fixed and immutable.

Question 8

Modern Synthesis

Answer 8

-describes the fusion (merger) of Mendelian genetics with Darwinian evolution that resulted in a unified theory of evolution. It is sometimes referred to as the Neo-Darwinian theory
• Between 1936-1947, Ronald A. Fisher and other scholars contributed to the integration of the fields of genetics, evolutionary biology, systematics, morphology, ecology, and quantitative statistics to create the Modern Synthesis.
• Other contributors to this synthesis include Theodosius Dobzhansky, J.D.S. Haldane, Julian Huxley, and G. Ledyard Stebbins.
• In 1942, Julian Huxley invented the term when he published his book, Evolution: The Modern Synthesis.
• While this synthesis is well understood today in the biological sciences, its application to human medicine is still emerging.

Question 9

Thomas Huxley

Answer 9

powerful voice in Britain 1970 in medical education policy

• he did not include evolution and comparative anatomy in med school cuz too much to learn already
• today evo med still lacks in med school education

Question 10

An evolutionary perspective broadens the way physicians and medical researchers think about health and disease

Answer 10

• Enhances quality of diagnosis and treatment of patients.
• Enhances our understanding of human populations and contributes to design of appropriate public health interventions.
• Helps identify important research questions to explore.

Question 11

Reasons evolution has not been included in medical education

Answer 11

• Crowded medical curriculum.
• Bias against the relevance of evolution in understanding health and disease.
• Lack of appropriately skilled faculty members in medical schools available to teach evolutionary principles.
• Up until recently, there has been a lack of appropriate, user friendly materials to teach the topic of evolutionary medicine.

Question 12

Microevolution

Answer 12

usually refers to slight relatively short term changes within a species.

Question 13

Macroevolution

Answer 13

usually meaning the evolution of substantial phenotype changes, typically great enough to place the changed lineage into a distinct new species or higher taxon.

Question 14

Trait

Answer 14

a distinct variant of a phenotypic character of an organism that may be inherited, environmentally determined, or be a combination of the two
• Traits typically result from the combined action of several genes, though some traits are expressed by a single gene (monogenic).
• No trait is perfect.
• Every trait must be analyzed in terms of the benefits and costs of the trade-offs inherent in a particular trait.
• Natural selection favors traits that improve the fitness (reproductive success) of individuals and their kin

Question 15

Fitness

Answer 15

=reproduction success
Selection operates to enhance fitness.
• Enhancement of fitness, does not necessarily operate to enhance health or longevity
• Fitness involves trade-offs which enhance reproductive success even if they incur other costs such as a shorter life.
• Evolutionary biology considers how an organism trades-off one component of its biology against others to enhance fitness.

Question 16

Proximate versus ultimate causes of disease

Answer 16

Most medical training focuses on understanding the immediate mechanistic pathophysiologic pathways leading to the disease, the so-called proximate causes.
• In this course we will explore the ultimate causes, the so called evolutionary factors which result in the emergence of pathways to health or disease.

Question 17

Ultimate causes of human disease and health

Answer 17

• How has evolution led to a particular trait or set of traits persisting?
• Is the trait helpful or not helpful under the present circumstances?
• Have the limits of acclimatization been exceeded due to a mismatch of evolutionary history, ancestral environment, and present environment?
The ultimate cause is the evolutionary explanation for why a person gets sick under certain circumstances.
• To understand the ultimate cause, the following questions must be asked:
• Why are some people prone to developing insulin resistance and type 2 diabetes mellitus?
• Why do certain populations carry a mutation in hemoglobin gene that causes some red blood cells to be sickle shaped?
• Why do some people develop pulmonary tuberculosis as a result of being exposed to tuberculosis while other people do not?

Question 18

Proximate causes

Answer 18

• The anatomical, physiological, molecular, and pathophysiological mechanisms that lead to a biological phenomenon.
• Insulin resistance leads to type 2 diabetes mellitus.
• Mutation in hemoglobin gene leads to sickle cell anemia.
• Exposure to tuberculosis may lead to pulmonary TB.

Question 19

Normal v Abnormal

Answer 19

Modern medical thinking has a tendency to dichotomize into normal or healthy and abnormal or unhealthy/pathological.
• However, such assessments are contextual: an adaptation (e.g., sickle cell) may prevent a certain disease (i.e., malaria) in a heterozygous carrier and thus make a person healthy, while this same adaptation puts a homozygous individual at risk for another disease (sickle cell crisis) and thus makes the individual unhealthy.
• We will explore these “trade-offs”in this course.

Question 20

Environment

Answer 20

physical, biological, and social world they live in.

Question 21

Development

Answer 21

which stage of development they are in.

Question 22

Physiology/anatomy

Answer 22

how they function in world.

Question 23

Behavior:

Answer 23

how they live in the world

Question 24

Transgenerational ancestral influences

Answer 24

mediated through genetic and cultural inheritance.

Question 25

Relevant histories | in systematic evolutionary framework

Answer 25

* #1: Medical history of the complaint/illness. * #2: Developmental history of the individual since conception. * #3: Evolutionary history of the individual’s lineage. * Hx of proband’s (person’s) population (including genetics, adaptations, isolation, migration, & drift) * Hx of hominin clade (including consideration of how our environment has changed) * Assessment of all these histories is essential for a comprehensive understanding of how an individual responds to their environment.

Question 26

Evolutionary Pathways to Health and/or Disease

Answer 26

• An evolutionary matched environment. • An evolutionary mismatched or novel environment. • Outcomes of demographic history. • Outcomes of cultural history. • Outcome of evolutionary constraints. • Sexual selection and “sexual”competition and their consequences. • Life-history and/or developmental associated factors. • Antagonistic pleiotropy. • A harmful allele when homozygous is maintained by heterozygote advantage. • Effects of deleterious allele does not become apparent until after reproductive age. • Spontaneous mutations for a deleterious gene defect replace alleles eliminated by selection. • Exaptation. • Excessive and uncontrolled defense mechanisms. • Fighting the evolutionary arms race with microbes.

Question 27

An evolutionary mismatched or novel environment

Answer 27

The biological processes that determine our present structure and function may have evolved in very different environments compared to those we now live in.

Question 28

An evolutionary mismatched or novel environment

Answer 28

Evolutionary change of our biological structure and function is slow while cultural evolution can cause our physical, nutritional, and social environments to change relatively quickly.

Question 29

Homo sapiens diet and level of exercise (mismatch)

Answer 29

The mismatch between the ancestral and contemporary diet and exercise regimes has resulted in dramatic increase in rates of obesity, insulin resistance, type 2 diabetes mellitus, and cardiovascular disease.

Question 30

Outcomes of demographic history

Answer 30

A person may now live in a different ecosystem/environment where the ancestral lineage adaptations may be maladaptive. • For example if a person with a evolutionary history of ancestors from a far northern latitude (e.g., Norway) migrates close to the equator, their level of skin melanin will be maladaptive to the high levels of UV radiation at equitorial latitudes. • Depending on where they migrated to, humans may have passed through population bottlenecks that generated founder effects.

Question 31

Outcomes of cultural history

Answer 31

- can influence what kind of food they eat - influences women's choice on how to approach labor and delivery - influence a women's choice to breast feed or not (will influence the health of the child)

Question 32

Results of evolutionary constraints

Answer 32

- bipedal walking | - larynx

Question 33

Bipedal walking

Answer 33

walking results in constraints on size of pelvic inlet/outlet in females which can make some newborn deliveries difficult.

Question 34

Larynx

Answer 34

• The change in shape and position of larynx necessary for human speech has resulted in increased likelihood of sleep apnea.

Question 35

Human life history trade offs

Answer 35

-The human life-course strategy is one of deployment of resources in the period up to peak reproductive performance, but trading-off that investment against the associated loss of reparative function in the post-reproductive period when a direct fitness advantage is not possible. • Thus the primary investment in maintenance and repair is prior to peak reproductive age and declines in post- reproductive years.

Question 36

Tradeoffs

Answer 36

emerge when stress in early life cues an individual to go into puberty early to increase the likelihood of reproduction, however earlier puberty has its inherent risks/cost

Question 37

Advancing puberty to increase fitness

Answer 37

can result in a mismatch between biological and psychosocial maturation -people who go into puberty early have a higher likelihood of getting depression and committing suicide

Question 38

Early-life events with late life consequences

Answer 38

infants with early nutritional stress are at greater risk for developing obesity, Type 2 diabetes, hypertension, and coronary artery disease as adults, especially if they grow up in a sedentary environment with abundant access to calories.

Question 39

Antagonistic pleiotropy

Answer 39

Traits that have been selected to have benefits in early life but then have detrimental effects later in life

Question 40

Example of antagonistic pleiotropy

Answer 40

- presence of stem cells in tissues which are adaptive during growth and reproduction to promote tissue maintenance and repair, but the persistence of certain stem cells can increase the risk of neoplasia (cancer) later in life.in life. - IGF-1 promotes fetal growth & muscle and skeletal growth during childhood and adolescence and fitness in early reproductive life, but later in life high levels are associated with an increased risk of certain cancers - testosterone enhances fitness in males in young years but later can increase risk of prostate cancer and heart disease

Question 41

Sexual selection

Answer 41

- Differential reproduction as a result of variation in the ability to obtain mates - Variation in the number of offspring produced as a consequence of a competition for mates.

Question 42

Sexual diphorphism

Answer 42

* Human males are on average taller and heavier than females. * Human males have a higher % of body mass as muscle compared to females. * However, humans have a relatively small degree of sexual dimorphism in body size and hence monogamous pair bonding rather than extreme polygyny has been and continues to be most typical for humans. * Some evolutionary biologists suggest that a mild partial-harem mating system may have been a norm in human evolution.

Question 43

Evolutionary pathways that enable alleles that cause monogenic disease to not be eliminated from the population

Answer 43

• Heterozygote advantage (e.g., sickle cell disease, cystic fibrosis, Tay-Sachs). • Effects of the deleterious allele may not become apparent until after peak reproductive age (e.g., Huntington’s chorea). • Recurrent mutation may retain a deleterious allele in the population (e.g., some forms of hemophilia).

Question 44

heterozygote advantage

Answer 44

- harmful allele when homozygous is kept by heterozygote advantage - The deleterious effects of the disease-promoting allele are confined to or expressed most strongly in homozygotes, but heterozygotes for the allele have some selective advantage and this causes the frequency of the allele to be maintained in the population.

Question 45

heterozygote advantage provides protection in the following ways

Answer 45

* Sickle cell allele protects against malaria * Cystic fibrosis allele protects against diarrhea and tuberculosis * Tay-Sachs allele protects against tuberculosis * Phenyketonuria allele: pregnant mothers who are carriers of this allele have lower spontaneous abortion rates and their fetuses are less likely to get cross-placental infection by the potentially fatal mycotoxin, ocratoxin A (see Woolf, Am J Hum Genetics, 1986, 38(5):773-5)

Question 46

effects manifest after peak reproductive age

Answer 46

* The effects of the deleterious allele may not become apparent until after peak reproductive ages, so the parent may pass on the allele to a child before negative selection has had a chance to operate. * An example of this is Huntington’s chorea/disease which has symptoms that typically do not emerge until middle age adult years. * Familial transmission accounts for more than 95% of new cases of Huntington chorea/disease.

Question 47

Spontaneous mutations for a deleterious gene defect replace alleles eliminated by selection.

Answer 47

* A deleterious allele is maintained in the population by recurrent mutation. * Even if copies of the deleterious allele are lost from the population because individuals carrying them die before reproducing, the allele is created anew at some finite rate by spontaneous mutation within the population.

Question 48

recurrent spontaneous mutations

Answer 48

* Examples of this includes some forms of hemophilia as well as some aneuploid conditions e.g., Trisomy 13, and Trisomy 18. * Hemophilia A (clotting factor VIII deficiency) and Hemophilia B (clotting factor IX deficiency) are the two most common forms of hemophilia and both are maintained by new spontaneous mutations that replace the alleles eliminated by negative selection. * Both are recessive sex-linked X chromosome disorders. * Since males have only one X chromosome, all males with the allele have hemophilia. * Females need to be homozygous with allele on both X chromosomes to have hemophilia; for this reason, it is rare in females.

Question 49

Excessive and uncontrolled | defense mechanisms

Answer 49

• Diseases of autoimmunity e.g., eczema, rheumatoid arthritis, and inflammatory bowel disease can be considered as situations where the normal evolved processes of defense are inappropriately and excessively activated causing person’s antibodies to attack their own tissues (autoimmune)

Question 50

Fighting the evolutionary arms race

Answer 50

* Humans are in a co-evolutionary relationship with viruses, bacteria, fungi, and parasitic diseases. * The short generation times of microorganisms compared to the long generation times of humans enables the microbes to evolve much more rapidly to attempt to out-compete human defense systems.

Question 51

Infectious diseases

Answer 51

• Host-pathogen interaction • Host-commensal interaction • Pathogen resistance • Pathogen virulence • Human host immune response • Human microbiome • Vaccinations • Antimicrobial medications • Emerging infectious diseases

Question 52

Niko Tinbergen’s 4 questions applicable to biological phenomena

Answer 52

``` #1: What is the mechanism underlying the phenomenon of interest? • #2: How does the phenomenon develop during the lifetime of the individual? That is, what is its ontogeny? (Ontogeny = the origin and development of an individual organism from embryo to adult) • #3: What is the function of the phenomenon? How does it serve the organism’s interests? • #4: How did the phenomenon evolve? What is its evolutionary history? Are there analogous phenomena in other species, and what is their evolutionary relationship to humans? What is the evidence for a selected origin? ```

Question 53

Question #1: what is the mechanism underlying the phenomenon of interest?

Answer 53

• Question #1 answer: the proximate mechanism is activation of the sympathetic nervous system fight/flight response which stimulates sweat glands to sweat.

Question 54

Question #2: How does the phenomenon develop during the lifetime of the individual? That is, what is its ontogeny? (Ontogeny = the origin & development of an individual organism from embryo to adult)

Answer 54

Question #2 answer: Sweat gland innervation is not completely mature until an infant is a few months of age. Also, the infant must be old enough to have the ability to perceive a threat that frightens and triggers the activation of the sympathetic nervous system fight or flight response. • Sweat glands are innervated in the early weeks after birth and the density of innervation and thus the capacity to sweat and tolerate extreme heat is influenced by whether or not an infant is brought up in a cold or hot environment. • This influences how an adult is able to sweat and tolerate heat.

Question 55

Question #3: What is the function of the phenomenon? How does it serve the organism’s interests?

Answer 55

• Question #3 answer: Sympathetic fight/flight activation generates increased heat in the body and the sweating is part of this response to help dissipate the excess heat and maintain normal body temperature.

Question 56

Question #4: How did the phenomenon evolve? What is its evolutionary history? Are there analogous phenomena in other species, and what is their evolutionary relationship to humans? What is the evidence for a selected origin?

Answer 56

Question #4: How did the phenomenon evolve? What is its evolutionary history? Are there analogous phenomena in other species, and what is their evolutionary relationship to humans? What is the evidence for a selected origin?