Evolutionary Medicine Flashcards
What philosophical cause is medicine concerned with?
The proximate or immediate cause:
The material cause - what it is aka table of wood
The efficient cause - does not change but interacts to cause the change - aka the father of a child
Is less concerned with the:
Formal cause - the shape or appearance of change - aka table
The final cause - the purpose of the change - to host a dinner party.
What is the difference between the final cause and the proximate ones?
Proximate - the most recent cause - how a behaviour works
Final - the first stepping stone in motion - why a behaviour exists.
What is a copy number variation?
A given genetic sequence, large or small, that repeats a variable number of times.
Can be in coding or non coding regions
Often shows normal polymorphism in the population, however same variation in repeat length can be considered a mutation.
What is a microsatellite in genetic terms?
A type of copy number variation
Small repetitive sequences that vary in length between individuals
Are non coding regions, may play a role in mRNA and gene splicing - helping to regulate gene expression.
Can become mutated.
What is the singular cause of genetic variation?
Mutation
What is the prevalence of variation in the human species?
0.2% of the genome is variant, the rest is the same between all individuals
Lowest variation from the globally shared genome is shown in Scandinavia and Europe.
Highest variation (smallest amount of shared variation) from the globally shared genome is seen in Africa
Why is Africa proposed to have higher levels of genomic variation compared to other continents?
Anatomically modern homo sapiens evolved 200,000yrs ago in Africa.
A small population of people migrated out of what will become modern day Africa and into other world regions.
These people are responsible for current population in other global regions, these new populations represented only a small proportion of the total human variation that was present in Africa.
Acted as a genetic bottle neck and reduced variation in other global regions.
What is the purpose of the pangenome?
Replaced the current genome project - which is a reference genome
Pangenome - aims to select geome for the fullest diversity of the human species possible.
What is the evolutionary origin underpinning covid?
Modern humans evolved from a common ancestor in Africa.
Homo sapiens and Neanderthals migrated out of Arfica around 800,000 years ago.
Modern non-Africans have neanderthal DNA in genomes - suggest some interbreeding outside of Africa.
The higher levels of neanderthal DNA in modern humans are found in South Asia, and the lowest levels in East Asia and Africa.
This is linked to a Denome Study of severe COVID-19 patients who were found to have more variation in chromoesme 3 immune genes compared to control group.
The locus of this DNA was inherited from neanderthals, therefore differential ancestoral inbreeding underpinned the geographical distribution of severe COVID 19.
What is the importance of regulatory DNA in evaluation and disease?
Most variation (single nucleotide polymporphisms) in the genome is found in non-coding, regulatory DNA such as promoters or enhancers.
95% of genetic disease is associated with non-coding DNA.
How does the evolutionary history or non-coding DNA make humans more vulnerable to disease?
Majority of humans enhancer (regulatory DNA) evolved at highest rates after split from chimpanzee common ancestor.
This is very true for neural specific enhancers which evolved rapidly in the human lineage only.
These regions of DNA are heavily association with cancer prognosis and inc nearby gene regions for age related disease.
What is the link between enhancer regions of DNA and humans risk of Alzhimers disease?
Increased expression of enhancer regions is correlated with decreased expression of a transcription factor (REST) that protects against Alzheimer’s disease.
These neural enhancers evolved rapidly after modern-day humans had divided from their common ancestry with chimpanzees, so are specific to modern humans -? why we are the only primates to get Alzheimers, trade off of evolution of the advanced human brain at the population level.
contrasting has increased expression of post-mortem AD brains
What is the link between evolution and autism?
Brain enhancer regions including HAR sequences evolved rapidly after human lineage split from chimpanzees.
HAR regions are expressed in fetal brain development and in the adult brain (brain function).
Mutations that affect HAR sequences is very strongly associated with being autistic.
Therefore evolving human brains predisposed us to autism.
Trade off with human evolution of advanced brain at the population level.
What si the evolutionary link behind Parkinsons Disease?
During evolutionary development, human cerebellum and cerebral cortex developed significantly to be elaborate and heavily folded.
However the human midbrain remained relatively small, this results in increased branching of axons that project from the midbrain to the cerebral cortex.
This puts a huge metabolic demand on neurons such as those found in the substantial nigra.
Therefore these neurons are at risk of dengeration, inc risk of Parkinsons Disease.
