College aantekeningen

Summary Evolutionary Medicine

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Rijksuniversiteit Groningen (RuG)

This summary covers: - A review of evolutionary genetics and dynamics - The co-evolution of parasites and hosts - Evolution of the immune system - Evolution and origin of human infectious diseases - Evolution of virulence – why are some infectious diseases fatal and others so mild that they ...

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Geupload op 12 april 2022
Aantal pagina's 29
Geschreven in 2020/2021
Type College aantekeningen
Docent(en) M.g. elliot
Bevat Alle colleges

selection
gene flow
genetic drift
evolution
genome size
red queen hypothesis
arms race
trade offs
genomic imprinting
kochs postulates

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Lecture 1
Beukeboom (chapter 1)

Introduction to evolutionary thinking

1. Genetic variation
2. Natural selection
- Not only surviving of the fittest but also
reproduction has to take place
3. Adaptation
- Trait that increases the ability of an organism to
survive and reproduce in specific environments
(Darwinian fitness)
4. Evolution
- A change over time in the genetic composition of
a population
- For this genetic variation is needed

Four necessary conditions for natural selection to act

1. Variation in the trait of interest
- Mice with different fur colours that are able to adapt better to different environments
2. The trait is heritable
- Almost all traits have the effect of the environment
- Come about through a combination between genetics and environment
3. Variation in reproductive success
- There is always reproduction and reproductive success
4. Some need a higher or lower reproductive success then others depending on the non-zero
correlation trait
- So the mice which are eaten the most by birds, because of fur colour, have to reproduce
at a higher rate in order to maintain their population

Forms of selection
- Sexual reproduction generates variation
- Asexual reproduction (clones)
o Offspring identical to parents except for
mutations
- 1 locus, 2 alleles
- Positive (directional) selection: selection against a
recessive lethal allele
o Directed to extreme alleles
o Increases the beneficial alleles
- Disruptive selection
o Both extreme alleles (homozygotes recessive or homozygotes dominant)
- Stabilizing selection
o Heterozygotes is in advantage
- Frequency-dependent selection
o Bright colours  dangerous traits, but they are preferable by females
o Positive: fitness increases when the frequency increases
o Negative: fitness decreases when the frequency increases

,Linkage disequilibrium = alleles are assorted according to their frequency in the population
- Reduced by recombination – recombination restores the equilibrium
- The combination of alleles are as what you would expect based on their frequency of the
population if there are no other factors (selection, environment) involved
- Locus A can have allele A or a
- Locus B can have allele B or b
- Crossing you would expect AA, Aa, aa
- If this is not the case  disequilibrium
- The case of Crohn’s disease  recombination decreases frequency
- Depends on physical distance, chromosomal position and configuration
o Increase in distance between genes causes an increase in disequilibrium and less
recombination
- Selective sweep = change in frequency of an allele due to selection on a closely linked
locus (also called hitchhiking)
- G6PD locus  glucose-6-phosphate dehydrogenase deficiency  helps against malaria
and therefore more present in African countries

Natural selection and evolutionary thinking
- Most of the time a very long process
- In some cases however it can be studied over a shorter period of time (bc changes and
adaption in some cases occur faster)
- Natural selection doesn’t have a goal to save a species in the future, but it can only work
backwards and work with the traits and variation already present
o Tinkering old pots together again to make one good new one

The study of evolution entails:
- Analysis of factors that change the number of copies of a gene in a population as they are
passed on (population genetics)
- Analysis of how genes produce traits that interact with the environment and therefor can
change (how genotype influences phenotype)
- The variants that persist aren’t necessarily the best possible
o Natural selection can only be applied on the traits that are already available
- Fitness = relative reproductive success

Five agents of evolutionary change

- Mutation

, - Gene flow
o Migration by individuals, take genes with them when moving to new population
- Non-random mating
o Increases the degree of homozygosity
o Increase in change of diseases
o 50% increase in homozygosity within one generation when there is 100% self-
fertilization
- Genetic drift
- Selection

Evolution of HIV
- Intracellular parasite of human macrophages and T-cells of immune system (uses cells
(infect it) to copy itself and kill the host cell)
- Immune cells start making copies of the virus
- There is a particular protein on the membrane of the T-cell which recognizes the binding
protein of the HIV virion, which allows the virus to enter the cell
- HIV RNA molecule is released in the host cell
- HIV reverse transcriptase makes RNA into DNA
- Treatment: azidothymidine
o Prevents binding of the next base by carrying N3  the virus cannot replicate
anymore
o Increased resistance to this drug by small mutations in reverse transcriptase,
which could detect the difference between regular thymidine and AZT
o Now get a variant through mutations which is partly resistant to AZT

Host-parasite interactions
- Virulence versus resistance
- Host
o Small population size
o Long generation time
o Low mutation rite
- All reverse for the parasite

Lecture 2 genome structures Beukeboom
Genome evolution = changes in genomic sequence, structure and function
- Point mutations
- Indels = deletions and insertions
- Synonymous = silent substitutions
o Faster rate
o No amino acid change
o Still encodes for the same proteins
- Non-synonymous = replacement substitutions
o Depends on protein complexity

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