Darwinian Medicine Flashcards
Germ theory of disease
Louis Pasteur
- contagious disease are caused by germs
- human sickness caused by microorganisms
1900 top causes of death
pneumonia, tuberculosis, diarrhea and enteritis
1997 top causes of death
heart disease, cancer, stroke
What helps us track disease?
phylogeny
____ are small; and single or double stranded
Genomes
RNA genomes
polio, flu, HIV, COVID-19
DNA genomes
herpes, smallpox
viruses features?
small size, genome in protein coat, replicate using host cellular machinery, no ribosomes
Are viruses alive?
“Life began the moment that molecules of information started to
reproduce and evolve by natural selection”
so, YES according to def.
Where did viruses come from: The progressive (or escape) hypothesis?
The progressive (or escape) hypothesis: Viruses arose from Transposable Elements (“jumping gene”, is a type of mobile genetic element that can change its position within a genome.)
Where did viruses come from: Regressive (or reduction) hypothesis?
Regressive hypothesis: viruses are remnants of cellular organisms that reduced themselves over time
Where did viruses come from: Virus-first hypothesis?
Virus-first hypothesis: Viruses pre-date the rest of the tree of life, or co-evolved with the tree of life
- The first replicating molecules likely consisted of RNA, not DNA (RNA World & Ribozymes)
- Perhaps simple replicating RNA molecules developed the ability to infect the first cells?
Three kinds of populations
- populations of a pathogen
- populations of cells in a host
- populations of the host
how are pathogens and hosts working against each other?
- pathogens are using the host to grow and reproduce; including spreading to new hosts..
- while the host is working to slow or stop the pathogen
Viruses have ____ population size, ____ generation times, ____ mutation rates
Large population size, short generation times, high mutation rates
Viruses with _____ transmission rate have the _____ fitness
highest; highest
Virulence
the harm done by a pathogen to a host during course of infection
Virulence can/cannot evolve?
CAN
How does virulence evolve?
- Coincidental evolution hypothesis
- Shortsighted evolution hypothesis
- Trade-off hypothesis
Influenze A
1918
killed 50-100 million people
Ways Hemagglutinin (protein on surface of flu pathogen) can infect?
- find naive host
- EVOLVE hemagglutinin so it becomes unrecognizable to antibodies in the host immune system (antibodies are only helpful if they match the hemagglutinin antigen that is presented in living flu virus/why there are different strands and flu vaccine isnt always helpful)
Antigenic sites
immune system can recognize these sites on a foreign protein (forms antibodies against antigens)
How does a virus create the kind of genetic diversity required to start a pandemic?
1) if two flu strains infect a single individual their RNA can combine; produces a variant mix of both strands “trade”
Why can different strands have similar nucleoproteins but unrelated hemagglutinin?
Flus strands can “trade” genes (example - Northern Territory)
The 1st strain of H3 in humans, and it caused the 1918 pandemic (Northern Territory/60/1968 (H3N3) describe the evolutionary point he was trying to make:
different virus genotypes recombined in a host to make a novel genotype in the virus that could evade immune systems and vaccinations
example: [pandemics can begin when human and bird strain infect a pig; genetic material is exchanged to create new strain, which can then re-infect people]
How does virulence evolve: Coincidental evolution hypothesis?
Coincidental evolution hypothesis: the virulence of a pathogen in humans may not be a target of selection, but an accidental byproduct (tetanus)
Coincidental evolution hypothesis example
Tetenus - caused by bacteria in soil (Claustridium tetani)
- bacterium produces neurotoxin; doesn’t normally infect humans, tetanus toxin evolved in soil —> virulence is high by coincidence (as if a human has contaminated wound by soil)
How does virulence evolve?
Shortsighted evolution hypothesis: Pathogens experience many generations of selection within a host before there is an opportunity for transmission to a new host.
Thus, traits that increase within host fitness may rise to high frequency even if they are detrimental to transmission (polio)
Shortsighted evolution hypothesis example?
Polio; originally infects cells in digestive tract - mild symptoms; spread through feces
- Polio sometimes invades nervous system –> may increase within host fitness {meaning, evolutionary advantage the virus could gain by strategy of invading NS}; but detrimental for humans (paralysis)
Polio cells in nervous system _____ transmitted to new host.
NEVER
Trade-off hypothesis?
All pathogens should evolve to be benign
- NOT CORRECT
- assumes the reproduction of a pathogen in a host does HARM; uses valuable energy and produces waste
- actually, some pathogens thrive when host is healthy, some thrive when host is very ill **
Viruses evolving to be benign (example with rabbits)
Viral disease of rabbits (Myxomatosis) mild disease in North American rabbits, deadly to European rabbits
- Ferrel rabbits cause environmental damage –> Myxoma virus introduced to kill rabbits off
- virus became LESS virulent; viruses that killed rabbits quickly weren’t transmitted easily to other rabbits (not effective) –> NATURAL SELECTION for reduced virulence
Natural selection for reduced virulence example
virus introduced to rabbits became less virulent because it wasn’t transmitted easily to other rabbits = not effective
Parasites transmitted by insects (e.g, malaria) or water (e.g., cholera) can thrive even when their host is very ill. Parasites that rely on ____ transmission cannot afford to be too virulent. Why?
direct (such as colds, flu, covid-19); sick people aren’t very interactive…
Vector borne diseases (e.g., by mosquitos) should be ____ (more/less) virulent than diseases that require direct contact for transmission
more virulent
Transmitted by close contact – mild
Transmitted by insects, water, food — very sick
cleaner water leads to evolution of ____ virulence (vice versa)
reduced virulence; due to clean water readily available, pathogens causing disease have less opportunity to spread in highly infectious manner; in contaminated water higher virulence due to easier transmission
Coronaviruses can infect many organs, but typically they infect the ______ and ______ tracts.
respiratory and GI tracts
What is the receptor for SARS-CoV-2 ?
ACE2 on lung cells
Variant
viral genome contains one or more mutations
when variant increases in frequency, due to either ____ or ____ selection
chance (genetic drift); positive selection ** suggests selection is involved, doesn’t prove (positive selection - variant provides fitness advantage, allowing individ. carrying that variant to survive and reproduce more successfully)
Variants more readily transmitted predominate. Explain this?
Variants better at spreading (longer survival, better adaptation to host, etc.) more common because they infect more people –> increasing frequency in population
higher transmissibility DOES NOT = more/or less virulent. Explain this?
Virulence: how sick individual is when infected
transmissibility: how efficient a pathogen infects new people
More transmissible variants can be LESS virulent (vice versa)
- higher transmission makes MORE people sick, doesn’t make them SICKER— may kill more people, even though less virulent
Variants (viral genome w/mutations) might make vaccines less efficient
Example - flu vaccine protects us against one strain of flu; variants are new strands of flu, our body doesn’t have the antibodies to fight new strains
What does evolution by natural selection relate to SARS-CoV-2 (and other viruses)
- variants are generated randomly by mutations
- some variants, by chance, spread and increase in frequency (higher evolutionary fitness)
Some examples of selection on viruses?
selection to…
- be more transmissible
- evade naturally-acquired immunity (hosts had prior infections; may have immunity to target virus – mutations allow virus to avoid defenses – inc ability to reinfect)
- evade immunity acquired by vaccinations
THERE IS NO CONNECTION BETWEEN A VIRUSES RATE OF SPREAD & HOW SICK IT MAKES YOU
don’t have to worry about individuals getting sick when new strains spread
Delta vs. Omicron mutations
Delta variant dominated bc specific mutations gave it advantages
Omicron variant has more mutations (# of mutations isnt as significant as which mutations occur) ** significant due to evolutionary distance from other variants
