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Homology
the quality of being similar or corresponding in position or value or structure or function
by common descent!!!
Parsimony
the simplest answer
humans and bacteria didn't arrive at this genetic code individually. they inherit it from previous ancestors, earlier organisms, who had that genetic code and now all organisms have it
Convergence
science is predicated on repeatability
a "built in test" for evolution
Virus
• Obligate intracellular parasites
• Two Parts:
Genetic Material (DNA or RNA)
Protein Capsid (surrounds genetic material)
• Sometimes present: Envelope (remnants of plasma membrane of a previously infected cell which aids entry to new cells for infection)
Influenza
• RNA Genetic Material
• Envelope Present
• Glycoprotein “spikes” that determine strain
• Influenza A:
H Spikes: finds receptors on host cell
N Spikes: Breaks down mucous membranes in the respiratory tract to make penetrating host cell easier
Naming Influenza Viruses
Host (if not human)
Type (A or B)
Strain, which H/N Spikes present
Year of Isolation
Viruses are not alive
• Viruses cannot process energy and rely on host cells to make copies of their genetic material
• Exception: Giant Viruses can make their own proteins
Infecting Cells
• Protein spikes are specialized to infect particular cell types
• Bind to surface proteins to allow virus entry
Viral Life Cycle
Attachment
Penetration
Biosynthesis
Maturation
Release
Lytic Cycle
• Virus begins biosynthesis/replication immediately
• Host cell is broken apart to release new virus capsids
• Influenza, common cold
Lysogenic Cycle
• Viral DNA integrates into host genome after penetration
• Virus remains inactive or latent, host cells divide with viral DNA integrated in genome
• Sickness occurs long after initial infection (HIV)
RNA Viruses
• Must use RNA polymerase to manufacture mRNA for protein synthesis
Many mistakes made by RNA Polymerase leads to mutations and fast viral evolution
Retroviruses
•Use reverse transcriptase to turn RNA into DNA before biosynthesis (HIV)
Influenza Infection
• Infects respiratory epithelial cells, replication begins immediately, leading to inflammation
• Body responds by sending immune cells which release cytokines, a chemical your body interprets as a warning signal of infection, leading to more inflammation
Influenza Symptoms
• Set in very quickly (over the course of an hour or two)
• Cough, fever, chills, aches and pains, headache, loss of appetite, nausea
Mostly caused by immune response, not the Influenza virus itself
• “Stomach flu” is NOT Influenza!
Spanish Flu Epidemic of 1918
• H1N1 virus killed between 1-5% of earth’s population
~20% of people infected died
Evolution
• A change in allele frequencies in a population over time
• Unifying theory of biology
“Nothing in biology makes sense except in the light of evolution.” - Theodosius Dobzhansky
• p² + 2pq + q² = 1
Georges Buffon (1707−1788)
Earth was much older than previously believed, which went against Church
Georges Cuvier (1769−1832)
Religious
Documented fossil discoveries (Irish Elk)
Jean-Baptiste Lamarack (1744−1829)
Living species might change over time
Believed acquired characteristics get passed on to offspring (wrong)
Charles Lyell (1797−1875)
Geologist
Uniformitarianism: all geological processes that happened in the past are still happening today
Geological forces had gradually shaped the earth
Charles Darwin
Born to a wealthy family
Fascinated by the natural world
Went to medical school and seminary school (transferred from Edinborough to Cambridge)
In 1831, joined the crew of the HMS Beagle for a five-year global surveying expedition
Voyage of the HMS Beagle
Observations from the Voyage of the Beagle
Island species have a strong resemblance to species on nearby mainland
Extant (living) species have a strong resemblance to extinct species discovered as fossils
Theory of Evolution by Natural Selection
Similarities between island/mainland species and living/fossil species could not be a coincidence
Overtime species that colonize new habitats gradually change to form new, but similar, species
Only the best-adapted individuals can reproduce, thus over time species become better adapted to the environment
Hesitated to publish
Darwin sat on his idea for decades because he didn't know the mechanism for heritability and he had 10 kids
Alfred Russel Wallace
Naturalist that explored South America and Indonesia
Sent paper to Darwin in 1858 postulating the exact same mechanism for species change
Joint Presentation to the Linnaean Society
Darwin and Wallace shared credit for the idea in a presentation in 1858
Darwin published his abstract in 1859: On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life
Darwin’s Postulates
Requirements for natural selection to lead to evolution:
There must be variation in a trait
The trait must be heritable from parent to offspring
The trait must lead to differential reproductive success
This differential reproductive success is not random, but rather tied to differences in heritable reproductive success
Condition 1: Variation for a Trait
Any gene with multiple alleles in a population has variability
Variation is the raw material of evolution; the engine of evolutionary change
Mutations
Changes in DNA sequences
Can lead to new alleles or new gene regulation mechanisms for selection to act upon
Mutations that increase the number of offspring an individual can produce will increase in frequency in the population over generations
Mutation rate in each gene is low, but they accumulate over time
Billions of years is loooong time
Where does a mutation need to take place to be passed on to the next generation?
Condition 2: Heritability
The trait must be passed from parent to offspring through genetic information (e.g., offspring inherit their traits from their parents)
Condition 3: Differential Reproductive Success
Individuals with one version of the trait must produce more offspring than those with a different version of the trait
Observations that led to this condition:
More organisms are born than can survive
Organisms continually struggle for existence
Some organisms are more likely to win this struggle to survive and reproduce
“Survival of the Fittest”
Fitness: A measure of the relative amount of reproduction of an individual with any phenotype
Survival + Reproduction rate
Alleles carried by an individual with high fitness will increase in a population over time
The population will evolve because the relative allele frequencies in this population are changing
Alleles that make you More Likely to Escape a Predator
Higher Red Blood Cell Count
Stronger muscle fibers
Higher bone density
Quicker nerve impulses
Intelligence to pick fastest escape route
Bigger lungs
Streamlined body shape
Better eyesight
Better hearing
Better sense of smell
Types of Natural Selection: Directional Selection
Individuals with one extreme from the range of variation will have higher fitness
Ex: Farmers only allow turkeys with the biggest breasts to mate
Types of Natural Selection: Stabilizing Selection
Individuals with intermediate genotypes will have higher fitness
Ex: Baby birth weight
Types of Natural Selection: Disruptive Selection
Individuals with extreme phenotypes experience the highest fitness, and those with intermediate phenotypes have the lowest
Evidence for Evolution
Fossil Record: Physical record of organisms that lived in the past
Comparative Anatomy and Embryology: Growth, development, and body structures of major groups of organisms
Molecular Biology: DNA similarities
Laboratory and Field Experiments: Use of the scientific method to study evolutionary mechanisms
Fossil Record
Hundreds of millions of fossils have been found
250,000 species
Hard parts get preserved
Teeth, bones, shells, seeds
Soft parts replaced by minerals
Traces: Imprints, tracks, burrows
Limitations:
Huge!
Biased in favor of abundant organisms with hard parts living in certain locations
Value
Transitional species
Comparative Anatomy and Embryology
Homologous structures reveal common evolutionary origins
If humans did not have bony fish ancestors, why do human embryos have gills early in development?
Developmental Regulatory Genes
Genes that activate protein coding genes early in development
Tell protein coding genes where to build body parts, but not HOW to build body parts
Great morphological diversity can be achieved with relatively small genetic change if that change occurs in developmental regulatory genes
HOX Genes
Low (or no) variation because all members of same species want bodies arranged in same manner
And all vertebrates want head, torso, and limbs in roughly the same spots
Highly conserved between species at high level
Differences only occur at levels telling embryo HOW to make body part
Hox Mutants
Very small genetic changes can result in enormous morphological differences
Makes morphological diversification much more likely to occur
The similarities in the bone structure of the forelimbs of mammals demonstrate...
common ancestry
Vestigial Structures
Apparently useless anatomical features reveal evolutionary past
Vampire bats still have molar teeth, even though the consume an all liquid diet
Convergent Evolution
Different starting organisms come to perform the same function through convergent evolution
Produces analogous structures
Molecular Biology
All living organisms have the same genetic code
DNA is more similar in more closely related organisms
Australian Marsupials and their Placental Counterparts
Laboratory and Field Experiments
Multigenerational experiments show evolution in progress
Evolution in Action
Fruit flies
Experimental Set Up
Results
Note: There is no way to differentiate between 20th percentile flies and 1st percentile flies in any generation.
Antigens
Spikes on virus capsid notify body that pathogen is present
Once identified, body knows exactly how to fight that virus if ever infected again in the future
What if the spikes change?
Evolution & Viruses
Viruses infect cells with what becomes loose genetic material – one cell simultaneously infected with multiple viruses can combine that DNA, easily creating new strains
Viruses mutate easily, creating new strains
Viral Evolution Requires Infected Hosts
SARS-COV-2 variants are all the result of evolution within infected hosts
Selection favors variants that are more transmissible and that evade protection from vaccines or previous infection
Viral Evolution: Antigenic drift
Small changes in surface spikes on virus makes it harder for immune system virus recognize it as a known pathogen (or make vaccines less effective)
Mutations caused by sloppy proofreading by copying enzymes
Viral Evolution: Antigenic Shift
Two forms of a virus infect the same cell, causing host cell to produce viral particles from both viruses, assembling a new strain with unique spikes
Immune System
Protects your body from foreign pathogens
Viruses, bacteria, toxins, eukaryotic parasites
Major Immune System Organs
Lymph Nodes: Filter pathogens from lymph fluid
Red Bone Marrow: Site of lymphocyte white blood cell production and (B-Cell) maturation
Spleen: Filter blood
Thymus: Site of T-Cell maturation
Self vs. Non-Self Recognition
Correct Major Histocompatibility Complex (MHC) Glycoproteins must be present on plasma membrane of cell
Natural Killer Cells: Kill cells not displaying correct MHC-I Glycoproteins
Innate Immune System
Immune system people are born with and requires no experience/prior exposure to work
Fast-acting, but not disease specific and it cannot defeat all pathogen types
Inflammation: Swelling, redness at site of wound or infection
White blood cells kill & remove pathogens, debris, dead cells
Clotting factors close wound to stop bleeding
Innate Immunity: Physical Barriers
Protect pathogens from entering body
Examples: Skin Mucous membranes Stomach Acid
Innate Immunity: Cytokines
Chemical signals of immune system that trigger other immune cells to fight pathogen
Example: Histamine Increases blood flow to region, increasing immune cell presence and preventing spread of pathogen (triggers inflammatory response)
Innate Immunity: Leukocytes
Phagocytize (engulf and kill) pathogens immediately upon arrival at infection site
Inflammatory Response
Damaged tissues secrete histamine, which increases blood flow to the area to deliver WBCs and clotting factor
Macrophages identify and destroy bacteria/viruses present
Neutrophils clean up the area
Clotting factors close wound
Adaptive Immune System
Fights specific pathogens, but cannot do so right away on first infection
You will get sick before this part of your immune system is working
-Has a memory
Once you’ve been infected by a pathogen, your immune system will remember how to recognize it in the future, creating a much swifter response
Antigens
Any substance that produces a specific immune response by the body
Flu: Protein Spikes
Usually pathogen-specific proteins or large carbohydrates
Adaptive Immune Response Step 1: Exposure To a Pathogen
Pathogen will have antigens on it, which help immune system recognize it
WBCs phagocytize pathogen, kill it, then take part of antigen to T-Cells, which begins adaptive response
Adaptive Immune Response Step 2: T-Cells Recognize the Antigens
T-Cells Mature in the Thymus
Cytotoxic T-Cells: Kill cells that have been infected by pathogen
Helper T-Cells: Take antigens to lymph nodes to present to B-Cells
B-Cells
Mature in Bone marrow
Produce antibodies to target specific pathogens
Release these antibodies into blood
Bind free-floating pathogens
Give all WBCs the ability to detect pathogen
Adaptive Immune Response Step 3: Immunity
Once B-Cells share antibodies, immune system targets pathogens and infected cells
Infection is defeated
Adaptive Immune Response Step 4: Memory
Once infection is controlled, B-Cells and T-Cells become memory cells
They don’t kill cells/look for antigens, but they remain in immune system waiting to see the antigens again
If re-exposed, the immune response can skip steps 1, 2, and 3 and just start killing infected cells and pathogens right away, so you won’t feel sick again
Vaccines
Exposure to a virus, bacteria, or toxin triggers a small immune response
Adaptive immune system means you won’t get the illness in the future
Usually an injection, but can be a pill
Sometimes you need regular boosters to keep immunity levels high
How Vaccines Work: Individual Level
Vaccines: Population Level
All infectious agents must spread to new hosts in order to survive and reproduce
Spreading requires susceptible people in population
If a population has high vaccination level, there aren’t enough potential hosts for spread to happen quickly (low probability of infected person meeting a susceptible person), aka Herd Immunity
R0, Basic Reproduction Number
Expected number of people to whom an infected individual will spread the illness if the entire population is susceptible
SAR-COV-2 R0 depends on variant
Alpha: ~2.5
Delta: ~7
Omicron: 8 - 12
Life Before Modern Vaccines
Outbreaks of disease would kill off whole families and decimate communities
Invention of Smallpox Vaccine
Eduard Jenner in 1796
Observed:
Milkmaids often were infected with cowpox, which was mild in humans
Milkmaids with cowpox NEVER had smallpox
Smallpox
Virus causing characteristic sores on body
30% of people who got it died
Globally eradicated by vaccination in 1980
Polio
Virus causes paralysis
Can attack diaphragm muscles (Iron lungs)
Often temporary, but not always
Eradicated by vaccination in America in 1994
Polio Vaccination
Measles
Virus causes extremely high (sometimes deadly) fever and a rash
Erases adaptive immune system!
Extremely contagious
Vaccine introduced in 1963
Types of Vaccines
Live Attenuated Virus
Toxoid
Component
Conjugate
Whole Killed Virus
mRNA
Live Attenuated Virus Vaccine
Live virus, but it is modified to be weaker
Not strong enough to cause you to be sick, but triggers immune response
Live virus replicates in your blood as part of this process
Immunocompromised people cannot get this type because their immune system isn’t strong to enough to fight off even the weakest virus
Examples: MMR, Chicken Pox
Toxoid Vaccine
Inactivated version of a bacterial toxin
The toxin produced by the bacteria is dangerous, not the bacteria
Examples: Diphtheria, Tetanus
Component Vaccine
Produced from just the surface antigen that triggers an immune response
Example: Hepatitis B
Conjugate Vaccine
Bacterial infections
Take plasma membrane sugars from bacteria and combine them with a protein the immune system recognizes as a pathogen
Example: Meningitis
Whole Killed Vaccine
Entire virus, but it is killed before being made into a vaccine
Still develop a strong immune response, but requires more boosters because the immune response is weaker than a live virus version
Immunocompromised people can get this kind of vaccine
Examples: Flu, Polio, Cholera, Typhoid
Influenza Vaccine
Whole killed virus vaccine or component vaccines
YOU CANNOT GET THE FLU FROM YOUR FLU SHOT!
Must enter production before flu season, so scientists predict the most likely strains the previous year
Sometimes they don’t predict well
mRNA Covid Vaccines
Injects mRNA enclosed in a lipid nanoparticle, allowing the host cells to make the viral protein for recognition by the immune system
Vaccine Development
Pre-Clinical Stage: Lab tests on animals
First In-Human Studies: Healthy adults only
Second In-Human Studies: Given to at-risk populations, like children
Phase 3 Studies: Large sample size testing under many conditions
Approval given by committee of public health experts and doctors before production for public begins (can take years and years)
Vaccine Skepticism
Smallpox vaccination became mandatory under the law in Europe and the US in the 1800s
Spawned many “Anti-Vaccination Leagues”
Current Vaccine Controversies
People believe vaccines cause autism
People believe vaccines have toxic ingredients
People believe children are given too many vaccines too quickly
People believe vaccines have side effects too severe to justify using them
Autism Spectrum Disorder
A group of developmental disorders that can lead to difficulty communicating or functioning
There is a huge range of symptoms, hence the “spectrum”
Temple Grandin
Professor of Animal Science at Colorado State University
Diagnosed with ”brain damage” as a child, diagnosed as Autistic in her 40’s
Public advocate for Autism research and rights
Revolutionized how cattle and other animals raised for meat are slaughtered
Pioneered humane handling based on animal behavior principles
Invented “hug box” to help people with sensory overload
Controversy: Autism and Vaccines
Study linking Measles-Mumps-Rubella Vaccine (MMR) to Autism published in English medical journal The Lancet in 1998 by Andrew Wakefield indicated that MMR vaccines cause autism
Study of 12 children
All received MMR & had intestinal abnormalities
8 of 12 developed autism
Wakefield recommended that Measles, Mumps, and Rubella be administered in three different shots
Vaccination Rates Dramatically decreased after the study was published
Other Studies Can Find absolutely No Evidence of A link Between Vaccines & Autism
Dozens of large studies preformed, none found any link No link with MMR No link with Mercury No link with vaccine schedule
Pooled together there were 1.25 MILLION children in these studies
Issues with Wakefield’s Study
When scientists and journalists compared the clinical records of the children in the study with Wakefield's paper, it was clear Wakefield has falsified his data for the paper
Wakefield also conducted his research unethically, performing colonoscopies, spinal taps, and barium meal tests on small children without permission
Undeclared Conflicts of Interest
Wakefield’s research was paid for by a lawyer in the process of suing pharmaceutical companies over the MMR vaccine
Nine months before he called for single measles vaccines, Wakefield filed a patent for one
He did not disclose either of these facts to the Lancet, which is required by ethics rules
Investigation and retraction
The Lancet retracted Wakefield’s paper in light of this information
This means the journal is essentially disavowing the article, meaning its results can’t be trusted and should not be cited by others
Wakefield lost his license to practice medicine in the UK