Evolutionary Medicine

Question 1

What is microevolution

Answer 1

• Evolution on a small scale
• Refers to the changes in allele frequencies within a single population
• Allele frequencies in a population may change due to four fundamental forces of evolution:
  
  • Natural selection
  • Genetic drift
  • Mutations
  • Gene flow

Question 2

Mutations roe in evolution

Answer 2

Mutations are the ultimate source of new alleles in gene pool

Question 3

WHta is Natural Selection

Answer 3

Some individuals with certain traits in a population have higher survival and reproductive rate than others and pass on these inheritable genetic features to their offspring.

• EVolution acts through natural selection whereby reproductive and genetic qualities that provide advantages to survival prevail into future generations
• The cumulative effects of natural selection process have giving rise to populations that have evolved to succeed in specific environments
• Naturla selection operates by differential reproductive success (fitness) of individuals.

Question 4

Darwins Finches diagram

Answer 4

It illustrates the way the finch ahs adapted to take advantage of feeding in different ecological niches

Question 5

WHat is Genetic Drift

Answer 5

• Random drift consists of random fluctuations in the frequency of appearance of a gene, usually, in a small population (Allele is defined as any one of 2 or more genes that may occur alternatively at a given site (locus) on the chromosome. Alleles are responsible for variations in a trait.
• The process of genetic drift may cause gene variants to disappear completely, thereby reducing genetic variability, even if they are beneficial traits that conduct to evolutionary and reproductive success.
• In contrast to natural selection, environmental or adaptive pressures do not drive changes due to genetic drift and the effects of GD is larger in small populations and smaller in large populations.
• Genetic drift is a stochastic process, a random event that happens by chance in nature that influences or changes allele frequency within a population as a result of sampling error from generation to generation.

Question 7

What are the population bottleneck and founder effect

Answer 7

• The population and a founder effect are 2 examples of random drift that can have significant events in small populations
• Genetic drift works on all mutations and can eventually contribute to the creation of a new species by means of accumulation of non adaptive mutations that can facilitate population subdivision.

Question 8

Describe the Bottleneck effect

Answer 8

• This occurs when there is a sudden sharp decline in a populations size typically due to environmental factors (natural diasters such as: earthquake or tsunamis, epidemics that can decimate the number of individuals in the population, predation or habitat destruction, etc)
• It is a random event, in which some genes (there is not any distinction) are extinguished from the population.
• This results in a drastic reduction of the total genetic diversity of the original gene pool
• The small surviving population is ocnsiderable be farther for the original one in its genetic makeup.

Question 9

A diagram to show the bottlenexk event and subsequent generations.

Answer 9

Question 10

WHat is the founder effect?

Answer 10

• Founder effect is the loss of genetic variation that occurs when a new population is established by a small number of individuals that are cleaved from a larger population
• This new population does not have the genetic diversity of the previous one
• Because the community is very small and also geographically or socially isolated, some genetic traits re becoming more prevalent in population
• This leads to the presence of certain genetic diseases in the next generation.
• In some cases, founder effects play a fundamental role in emergency of new species.

Question 11

An image to highlight the founder effects and description

Answer 11

Question 12

what is a mutation

Answer 12

• Mutation can be defined as a change in the DNA sequence within a gene or chromosome of a living organism
• Many mutations are neutral, i.e. they can neither harm nor benefit, but can also be deleterious or beneficial
• Deleterious mutations can affect the phenotype and in turn, reduce the fitness of an organism and increase the susceptibility to several illnesses and disorders
• On the other hand, beneficial mutations can lead to the reproductive success and adaptability of an organism to its environment
• These beneficial mutations can be spread and fixed in the population due to natural selection processes if they help individuals in the population to reach sexual maturity and to successfully reproduce
• Mutations are, undoubtedly, a source of genetic variation and serve as a raw material for evolution to act
• Germ line mutations occur in gametes (eggs or sperm cells) and can be pass on to offspring, whereas somatic mutations occur in non-reproductive cells and are not pass on to the following generation
• Those mutations that occur in germ line are the most important to large-scale evolution because they can be transmitted to offspring

Researchers at the New York Genome Center (NYGC) and Columbia University’s Department of Systems Biology have uncovered a molecular mechanism behind one of biology’s long-standing mysteries: why individuals carrying identical gene mutations for a disease end up having varying severity or symptoms of the disease.

Question 14

Are mutations planned and what are the 3 different groups?

Answer 14

Mutations can be spontaneous (errors during a normal process of DNA replication, spontaneous lesions and transposable genetic elements), but they can also be induced by numerous external or exogenous factors like environmental chemical agents or ionizing radiation, for example

According to their magnitude (mutations can occur at different levels), they can be divided into three different groups:

▪ Gene mutations: any change in the sequence of nucleotides of the genetic material of an organism

▪ Chromosome mutations: a change in the structure or arrangement of the chromosomes

• Duplications or deletions of chromosome segments
• Inversions of sections of DNA (reversed positions)
• Translocation

▪ Genome mutations: alterations in the number of chromosomes in the genome

Question 15

WHat are genome mutations and the 2 groups of them?

Answer 15

Genome mutations = alterations in the number of chromosomes in the genome

• Aneuploidy - Losses and/or gain of individual chromosomes from the normal chromosome set arising from errors in chromosome segregation
• Euploidy - refers to variations in complete sets of chromosomes

Question 16

Gene Flow

Answer 16

• In population genetics, Gene Flow (also known as gene migration) refers to the transfer of genes from the gene pool of one population to another
• Gene flow may change the frequency and/or the range of alleles in the populations due to the migration of individuals or gametes that can reproduce in a different population
• The introduction of new alleles increases variability within a population and allows for new combinations of traits

Question 17

Horizontal Gene transfer (HGT)

Answer 17

HGT = also known as lateral gene transfer (LGT) is a process in which an organism (recipient) acquireds genetic material from another one (donor) by asexual means

Already known that it has played major role in evolution of many organisms kike bacteria

Question 18

WHat is evolutionary science. biology

Answer 18

• Evolutionary science = the fundamental “organizing principle” of all biology
• The biological and biomedical sciences can only be fully integrated with the aid of an evolutionary toolkit
• Evolutionary biology provides the basis of our understanding both of the function of an organism and of its relationship with its physical, social, and biotic environment
• An effective comprehension of human biology,health, and disease requires knowledge of evolutionary principles and an appreciation of how they have shaped biological and biomedical processes at both an individual and population level
• Although this imperative is well appreciated in the other biological sciences, medicine has been slow to recognize evolutionary biology as a fundamental and underpinning science
• However, advances in areas such as bacterial evolution, genomics, and epigenomics mean that evolutionary thinking has much to add to modern medicine

Question 19

Evolutionary biology has to address many questions- what are these

Answer 19

▪ How species have formed?

▪ How lineages respond to and adapt to their environment and thus evolve to appear to be “designed” to match their environment?

▪ How environmental influences induce the development of a range of phenotypes from a single genotype?

▪ Why different species even within the same taxa have very different physical, reproductive, and social characteristics?

▪ Why species have particular life histories?

The answers to these questions inform our understanding of the origin of the particular characteristics of a species and the range of phenotypic variation seen between individual members of that species- in particular in their anatomy and their physiology, the characteristics of their life course, and the manner in which they respond to environmental challenge and opportunity

Question 20

How medicine and public health can utilize the basic principles of evolutionary biology?

Answer 20

• Most members of the health professions have had little or no formal exposure to such principles (deficiency!?)
• Thus evolutionary biology is very much concerned with the basis and the significance of individual variation
• Humans, like all other living organisms, have individual characteristics, including the fact that we do not all suffer from the same diseases (this variation is defined in part by our evolutionary history)
• To understand human biology and medicine fully, we must have an understanding of evolutionary principles and how they apply to our species
• Much of medicine is focused on understanding:
  
  • ▪ Disease causation
  • ▪ How to prevent disease
  • ▪ How to intervene when it does occur
• Medical thinking has a tendency to dichotomize into normal or healthy and abnormal or pathological
• Successful adaptation in one context, and so normal under those conditions, may be highly abnormal in another

Question 22

The definition of what is health and what is disease when viewed through an evolutionary lens can therefore lead to helpful new perspectives on a potential patient

How is variation fundamental?

Answer 22

Variation is a fundamental attribute of biology, and it determines individual risk in response to an environmental challenge whether:

▪ This is a parasite like malaria?

▪ An environmental toxin like nicotine

▪ A lifestyle of excessive calorie intake

How individual risk is determined by our evolutionary history and how that history has given us a capacity to cope with many challenges but has also placed constraints on that capacity

The consequences of encountering challenges which exceed our adaptive capacity become manifest as disease.

Question 23

How medical training focuses on understanding the immediate pathways leading to disease- these are so-called proximate causes

Answer 23

From this perspective:

▪ Hypertension arises because of changes in peripheral vascular resistance or because of changes in the renin–angiotensin system secondary to renal disease

▪ Sickle cell anemia arises because of a mutation in the hemoglobin gene

▪ Appendicitis arises because of inflammation in a gastrointestinal diverticulum

▪ Cerebral palsy can arise because of asphyxia at birth during an obstructed labor

It is this understanding of proximate cause that gives rise to most medical therapies: serotonin reuptake inhibitors to treat depression, antibiotics to treat

bacterial pneumonia, angioplasty to improve blood flow through occluded coronary arteries, or cesarean section….. But in each case there is a broader dimension.

The proximate explanations reveal how certain symptoms appear and provide the basis of a logical approach to intervention, but there is a further level of enquiry which is valuable

This concerns questions about:

▪ Why certain symptoms appear?

▪ Why some individuals are at greater risk?

▪ Why we cannot accommodate easily to certain situations healthily?

▪ Why we have an appendix which gets inflamed?

▪ Why the day you are born was the most dangerous day of your life so far?

Question 24

Sign RA

Answer 24

Question 25

What does the evolutionary level of interrogation seeks to understand

Answer 25

* This evolutionary level of interrogation seeks to understand the ultimate causes of health and disease * Through it, we discover that we get appendicitis because our evolutionary ancestors were leaf-eaters and had a large cecum to help digest cellulose-based foods; we now no longer need this large gastrointestinal organ, but the appendix remains as an evolutionary relic which can become inflamed * This ultimate perspective provides health professionals with better insights into their patient and must improve their management of the case * In many instances an evolutionary perspective leads to a better understanding of which approaches to prevention are more promising and why certain therapies are more likely to work * Humans now live in very complex environments which are very different from those in which most of our ancestors lived and evolved * The consequent mismatches can challenge our health * We can never escape our biology or our biological past * Evolutionary processes operate to promote passage of genetic information from one generation to the next and evolutionary success is about successful passage of genes within a lineage to future generations

Question 26

Is EVolutionary medicine essential?

Answer 26

* Evolutionary medicine, therefore, is a growing and central discipline that applies evolutionary knowledge to the understanding of human biology, both normal and abnormal * It is an essential science, necessary for a holistic perception of how health and disease emerge * It has application in both individual healthcare and in public health * It adds much to understanding other basic disciplines of medicine, including physiology, anatomy, biochemistry, pathology, molecular biology, population health, and behavioral sciences

Question 28

Core principles for evolutionary medicine - how they agreed them

Answer 28

Question 29

Core principles of evolutionary medicines - agreed by panelists

Answer 29

1. Types of Analyses (100% agreement) 2. Evolutionary processes (100% agreement) 3. Reproductive success (96.6% agreement) 4. Sexual Selection (80% agreement) 5. Constraints on natural selection (90% agreement) 6. Trade-offs (96.5% agreement) 7. Lif ehsitory theory (100% agreement) 8. Multiple levels of selection (86% agreemnt) 9. Phylogency (88.5% agreement) 10. Coevolution (96.5% agreement) 11. Plasticity (96.5% agreement) 12. Defenses (93% agreement) 13. Mismatches (93% agreement) 14. Cultural Practices (100% agreement)

Question 30

Ecolutionary processes

Question 31

Types of Analyses - As a core principle of evolutionsry medicine

Answer 31

**Types of Analyses(100% agreement) :** * Both proximate (mechanistic) and ultimate (evolutionary)explanations are needed to provide a full biological understanding of traits, including those that increase vulnerability to disease * Understanding evolutionary medicine requires understanding the kinds of questions asked in the field, especially the difference between proximate and evolutionary explanations. * Regardless of wording, this principle provides an essential foundation for recognizing the several complementary kinds of explanations that can be used across the life sciences * (Nature-genes and hereditary vs Nurture-environmental variables)

Question 32

Evolutionary Processes as a core principle of evolutionary medicine

Answer 32

**Evolutionary Processes (100% agreement): PIC** * All evolutionary processes, including natural selection, genetic drift, mutation, migration and non-random mating, are important for understanding traits and disease * Many panelists made comments about the importance of recognizing the contributions of all four processes in order to avoid the error of considering only natural selection * Understanding evolution in depth is fundamental to evolutionary medicine, and this principle, while written to be general, captures how an understanding of all evolutionary processes is central to evolutionary medicine

Question 33

Reproductive success as a core principle of evolutionary medicine

Answer 33

**Reproductive Success (96.6% agreement):** * Natural selection maximizes reproductive success, sometimes at the expense of health and longevity * Initial survey responses included both general comments about the process of natural selection, as well as comments that specifically emphasized that natural selection selects for reproductive fitness, which can occur at the expense of health and longevity * While we initially considered these overlapping principals (an understanding of natural selection free of misconceptions should include knowing that reproductive success can be at the expense of health and longevity), panelist comments and ratings indicated that a separate focus on reproductive success is an important and distinct core principle

Question 34

Sexual Selection (80% agreement) as a core principle of Evoluntionary Medicine

Answer 34

* Sexual selection shapes traits that result in different health risks between sexes * Like the principle for reproductive success sexual selection can be considered nested within a general understanding of natural selection * However, most panelists recommended including sexual selection as importatant separate core principle * Understanding how sexual selection shapes differences in male and female phsyiology and behaviour is important for understanding differences in health risks

Question 36

Constraints on natural selection (90% agreement)

Answer 36

* Several constraints inhibit capacity of natural selection to shape traits that are hypothetically optimal for health * They include path dependence, the inevitability of mutations, trade-offs such those seen in antagonistic peliotropy and others * This is a principle with large scope, and large ideas in evolutionary medicine nested within it * The vague wording of this principle led to some concerns about its importance but most panelists saw this idea as an important idea for the field

Question 37

Trade offs as part of core principle of evolution

Answer 37

* Evolutionary changes in one trait that improve fitness cna be linked to changes in other traits that decreases fitness * The role of evolutionary trade-offs in explaining disease vulnerability is a central and important core principle for evolutionary medicine * The principle is intimately tied to life hisotry theory, and has been a major and influential idea in evolutionary medicine and beyond * Indeed, some panelists felt that LHT was a nested principle that could be understood through trade-offs, while others saw this relationship in the inverse (trade-offs as subset LHT) * While this principle achieved high agreement in its current form, it could be somewhat misleading by implying that trade-offs must include two traits An alternative wording could be ‘Evolutionary changes in a trait that improve fitness can often also decrease fitness’ For instance, lower levels of gastric acid reduce ulcers at the cost of increased risk of infection

Question 39

Life history theory (100% agreement)

Answer 39

* Life history traits, such as age at first reproduction, reproductive lifespan and rate of senescence, are shaped by evolution, and have implications for health and disease * The evolution of life history traits is intricately tied to many aspects of health * Understanding the evolutionary origins of human life history traits such as altriciality (altricial species are those species whose newly hatched or born young are relatively immobile, lack hair or down, are not able to obtain food on their own, and must be cared for by adults), short inter-birth intervals and prolonged maturation time are critical for understanding life-stages and health outcomes

Question 40

Multiple levels of selection as core principle evolution

Answer 40

* Vulnerabilities to disease can result when selection has opposing effects at different levels (e.g. genetic elements, cells, organisms, kin and other levels) * Responses to the initial survey suggested listing somatic selection in cancer, genetic conflicts and mentions of group selection as core principles * While these concepts differ in their implications for health and disease, they share a larger focus on thinking about selective dynamics at levels other than the individual * That is, natural selection can act on replicating entities at different levels, and when the selection forces differ between these levels, conflict can occur * Thus, understanding cancer through an evolutionary lens requires considering the how selective dynamics at the cellular level interact with those at the individual level * Similar reasoning is needed to understand the evolutionary dynamics of genetic element replication at a cost to the cell

Question 41

phylogeny as core principle evolution

Answer 41

* Tracing phylogenetic relationships for species, populations, traits or pathogens can provide insights into health and disease * While neglected early on in evolutionary medicine, tracing phylogenetic relationships is a major area of evolutionary research that is becoming increasingly important for evolutionary medicine * While phylogenies often focus on the relation between species, comments from panelists indicated that phylogenies of populations, different molecules or traits and pathogens, are all useful for medical research * This core principle encompasses the importance of understanding the relatedness between any replicating entities

Question 42

Coevolution as core principle of evolution

Answer 42

* Coevolution among species can influence health and disease (e.g. evolutionary arms races and mutualistic relationships such as those seen in the microbiome) * Understanding many human diseases requires appreciating the coevolution between pathogens and defenses against those pathogens * Indeed, most antibiotics are produced by bacteria as a result of co-evolutionary competitions with viruses and other bacteria * Notably, coevolution is also an important consideration for the emerging field investigating the roles of microbiomes in health

Question 43

Plasticity as core evolution principle

Answer 43

* Environmental factors can shift developmental trajectories in ways that influence health and the * Plasticity of these trajectories can be the product of evolved adaptive mechanisms * Plasticity is a general capacity of living organisms—phenotypes shift in the course of development or over shorter time frames as genes interact with varying environments * Plasticity is important to evolutionary medicine because selection shapes mechanisms that regulate plasticity that can influence disease risks * Especially important for medicine are mechanisms that shift development in response to * environmental cues detected during * developmental windows

Question 44

Defences

Answer 44

* Many signs and symptoms of disease (e.g. fever) are useful defenses, which can be pathological if Dysregulated * Evolved defenses as a concept has a more narrow focus than some of the other principles, but it is centrally important to how evolution can inform medicine * Understanding signs and symptoms of disease as protective responses has implications for Treatment * How selection shapes systems that regulate defense expression (the Smoke Detector Principle) was considered as a separate principle but was incorporated into this larger category

Question 45

Mismatch as core evolutionary principle

Answer 45

* Disease risks can be altered for organisms living in environmentsthat differ from those in which their ancestors evolved * Comments throughout the Delphi study necessitated edits to ensure that this principle captured the various ways mismatch can occur (e.g. moving to a new environment, a past environment changing rapidly, etc.) * It is also important to avoid the incorrect assumption that humans are adapted to a single environment, and to recognize that mismatch may result from migration between stable environments

Question 46

Cultural practices - core evolutionary principle

Answer 46

* Cultural practices can influence the evolution of humans and other species (including pathogens), in ways that can affect health and disease (e.g. antibiotic use, birth practices, diet, etc.) * Understanding any aspect of human traits requires considering the importance of culture and cultural practices * This importance includes the evolutionary impacts of medical practices such as antibiotic use, chemotherapy regimens and caesarean sections * This principle can incorporate the importance of many behaviors and traits not attributable to genetics, but possibly involving cultural practices

Question 47

Principles not meeting consensus

Answer 47

* Many principles nominated by the panelists either did not achieve 80% consensus regarding their importance to evolutionary medicine, and one (natural selection) was above this threshold but a similar core principle (Reproductive success) was at a higher consensus * While the lower ratings of these principles resulted in their exclusion from the final list of core principles * Indeed, while these principles did not make the final list, many of them may still be of interest to instructors in creating learning goals in courses focused on related topics * Notably, some of the principles in this list could be considered more uniquely relevant to evolutionary medicine than other broader core principles * As an emergent and growing field, this may change over-time

Question 48

Suggested principles that didnt reach 80% consensu in core evolutionary principles

Answer 48

Question 49

Answer 49