Evolutionary Medicine
Lecture 1, 27/2/2023, Evolutionary Principles and Processes
Written exam 30%, MC exam 30%, Poster 40%
Evolutionary thinking related to health.
Genes are a conceptual construct; alleles are real things.
The “central dogma” of molecular biology: transcription, translation
- DNA, mRNA, protein
Complete dominance → a situation in which one allele completely masks the effect of the
other allele.
Incomplete dominance → a situation in which neither allele masks the other; both alleles
are expressed and generate an intermediate phenotype.
Codominance → both phenotypes are present.
Heterozygotes generally perform better than homozygotes → overdominance → the
phonotype of the heterozygote is outside the range of the homozygote parents.
Epistasis interactions → the interaction of alleles at different loci.
Evolutionary fitness → a concept used to express the degree to which a biological entity
makes copies of itself in the next generation.
Four necessary conditions for natural selection to act.
1. Variation in the trait of interest
2. Variation is heritable.
3. Variation in fitness
4. A correlation between the trait and fitness
Hardy-Weinberg equilibrium → no change in allele frequency over time.
- p2 + 2pq + q2 = 1
A recessive mutation is less visible in the population making for less natural selection.
It is best to be the rare color in flowers, so the bees still visit.
Genetic drift → population size is an important determinant of the strength of selection.
Assortative mating → the tendency of similar individuals to mate with each other.
Demography → migration leads to the introduction of novel alleles into the population,
resulting in deviation from Hardy-Weinberg
- ‘Demographic structure’ → non-random distributions of gametes resulting from a
population being split into sub-populations who usually mate together.
,Lecture 2, 27/2/2023, Evolutionary thinking applied to human health
Traditional medicine → how questions
Evolutionary medicine → why questions
Why do we get sick?
Evolutionary processes resulting in sub-optimal outcomes → why we can have illnesses like
cancer
1. Selection is too slow
a) Mismatch between design and environment → traits that were adaptive during
evolution can become maladaptive after rapid environmental change.
b) Accumulation of mutations → adaptation to pathogens by the host can be
‘swamped’ by new mutations.
2. Selection is too fast
a) Trade-offs between different biological
b) Trade-offs between different times of life
c) Constraints on what is actually evolvable
3. We misunderstand what selection shapes
a) Natural selection does not necessarily favor being happy and healthy
b) Some diseases may actually be unpleasant adaptive responses
Studies in a Hutterite community indicate that each person carries two recessive lethal
alleles → lethal in homozygotes, harmless in heterozygotes
Lecture 3, 28/2/2023. Genetic Conflicts
Conflict between mitochondrial and nuclear genomes → mitochondria arose from a
prokaryote
Natural selection favors cells that maintain the integrity of their nuclear genome, also the
faster dividing cells.
Selection for rapid mitochondrial division has resulted in the mitochondrion shrinking over
time → a lot of genes become useless and are lost over evolutionary time
NUMT → Nuclear mitochondrial gene → all genes necessary for mitochondrial function
- When entering the functional regions of the genome of the human they can cause
diseases
Competition between mitochondrial is harmful to the animal, because it is a waste of energy
and there is danger of mitochondria attacking each other.
Parent-offspring conflict → how much energy/maternal investment the parent puts into the
offspring
Fetal optimum → the level of investment that the fetus wants to receive from its mother
- Investing 0.6 units
- For the mother investing 0.2 units is better
Parent-offspring conflict results from differences in relatedness between family members
, Hamilton’s rule → carry out an altruistic act when the costs (c) of the act are less than the
benefits (b) of the act multiplied by the relatedness (r).
- Act altruistically when br > c
Pregnancy is maintained via the production of LH and LH’s stimulation of progesterone
production.
- Anterior pituitary → corpus luteum →uterus
hCG (from embryo) bypasses this pathway and stimulates the corpus luteum to produce
progesterone and by the 8th week of pregnancy, produces enough progesterone to sustain
pregnancy on its own.
For the fetus, natural selection favors the strongest reaction possible, 100x more than is
necessary for reproduction → causes conflict, because it causes morning sickness in the
mother.
Conflicts over food for the growing fetus
Pre-eclampsia → disruption of the conflict system, causing extremely high blood pressure in
the mother, can be lethal
Mother rejects the baby more often than the baby rejects the mother.
How parent-offspring conflicts contribute to disease
1. Disruption of ‘tugs-of-war’ over resources
2. Wastes of resources
3. Maladaptation in party that ‘loses’ in a conflict
4. Within-family ongoing verbal, physical conflicts
Selfish offspring is a disadvantage for later mutations
Beneficial when males passes it on to its sons, but harmful when passed on to daughter,
because she will have selfish offspring
- Switching of the maternal copy prevents the mother from having selfish offspring
Genomic imprinting →expression of a gene depending on whether inherited from father or
mother, genes are switched of in a parent specific matter, the imprinted gene is the silenced
one.
Why genomic printing has evolved in placental mammals is related to conflict.
Genomic imprinting in pregnancy
1. Silenced when inherited from either the father or the mother
2. Paternally expressed genes are expected to be associated with increased demands
on the mother, by offspring (IGF2)
3. Maternally expressed genes are expected to be associated with reduced demands on
the mother (IGf2R)
Genomic imprinting is one means of resolving conflict, one party switches of a gene, the
other party can set the valued trait to an optimum.
Lecture 1, 27/2/2023, Evolutionary Principles and Processes
Written exam 30%, MC exam 30%, Poster 40%
Evolutionary thinking related to health.
Genes are a conceptual construct; alleles are real things.
The “central dogma” of molecular biology: transcription, translation
- DNA, mRNA, protein
Complete dominance → a situation in which one allele completely masks the effect of the
other allele.
Incomplete dominance → a situation in which neither allele masks the other; both alleles
are expressed and generate an intermediate phenotype.
Codominance → both phenotypes are present.
Heterozygotes generally perform better than homozygotes → overdominance → the
phonotype of the heterozygote is outside the range of the homozygote parents.
Epistasis interactions → the interaction of alleles at different loci.
Evolutionary fitness → a concept used to express the degree to which a biological entity
makes copies of itself in the next generation.
Four necessary conditions for natural selection to act.
1. Variation in the trait of interest
2. Variation is heritable.
3. Variation in fitness
4. A correlation between the trait and fitness
Hardy-Weinberg equilibrium → no change in allele frequency over time.
- p2 + 2pq + q2 = 1
A recessive mutation is less visible in the population making for less natural selection.
It is best to be the rare color in flowers, so the bees still visit.
Genetic drift → population size is an important determinant of the strength of selection.
Assortative mating → the tendency of similar individuals to mate with each other.
Demography → migration leads to the introduction of novel alleles into the population,
resulting in deviation from Hardy-Weinberg
- ‘Demographic structure’ → non-random distributions of gametes resulting from a
population being split into sub-populations who usually mate together.
,Lecture 2, 27/2/2023, Evolutionary thinking applied to human health
Traditional medicine → how questions
Evolutionary medicine → why questions
Why do we get sick?
Evolutionary processes resulting in sub-optimal outcomes → why we can have illnesses like
cancer
1. Selection is too slow
a) Mismatch between design and environment → traits that were adaptive during
evolution can become maladaptive after rapid environmental change.
b) Accumulation of mutations → adaptation to pathogens by the host can be
‘swamped’ by new mutations.
2. Selection is too fast
a) Trade-offs between different biological
b) Trade-offs between different times of life
c) Constraints on what is actually evolvable
3. We misunderstand what selection shapes
a) Natural selection does not necessarily favor being happy and healthy
b) Some diseases may actually be unpleasant adaptive responses
Studies in a Hutterite community indicate that each person carries two recessive lethal
alleles → lethal in homozygotes, harmless in heterozygotes
Lecture 3, 28/2/2023. Genetic Conflicts
Conflict between mitochondrial and nuclear genomes → mitochondria arose from a
prokaryote
Natural selection favors cells that maintain the integrity of their nuclear genome, also the
faster dividing cells.
Selection for rapid mitochondrial division has resulted in the mitochondrion shrinking over
time → a lot of genes become useless and are lost over evolutionary time
NUMT → Nuclear mitochondrial gene → all genes necessary for mitochondrial function
- When entering the functional regions of the genome of the human they can cause
diseases
Competition between mitochondrial is harmful to the animal, because it is a waste of energy
and there is danger of mitochondria attacking each other.
Parent-offspring conflict → how much energy/maternal investment the parent puts into the
offspring
Fetal optimum → the level of investment that the fetus wants to receive from its mother
- Investing 0.6 units
- For the mother investing 0.2 units is better
Parent-offspring conflict results from differences in relatedness between family members
, Hamilton’s rule → carry out an altruistic act when the costs (c) of the act are less than the
benefits (b) of the act multiplied by the relatedness (r).
- Act altruistically when br > c
Pregnancy is maintained via the production of LH and LH’s stimulation of progesterone
production.
- Anterior pituitary → corpus luteum →uterus
hCG (from embryo) bypasses this pathway and stimulates the corpus luteum to produce
progesterone and by the 8th week of pregnancy, produces enough progesterone to sustain
pregnancy on its own.
For the fetus, natural selection favors the strongest reaction possible, 100x more than is
necessary for reproduction → causes conflict, because it causes morning sickness in the
mother.
Conflicts over food for the growing fetus
Pre-eclampsia → disruption of the conflict system, causing extremely high blood pressure in
the mother, can be lethal
Mother rejects the baby more often than the baby rejects the mother.
How parent-offspring conflicts contribute to disease
1. Disruption of ‘tugs-of-war’ over resources
2. Wastes of resources
3. Maladaptation in party that ‘loses’ in a conflict
4. Within-family ongoing verbal, physical conflicts
Selfish offspring is a disadvantage for later mutations
Beneficial when males passes it on to its sons, but harmful when passed on to daughter,
because she will have selfish offspring
- Switching of the maternal copy prevents the mother from having selfish offspring
Genomic imprinting →expression of a gene depending on whether inherited from father or
mother, genes are switched of in a parent specific matter, the imprinted gene is the silenced
one.
Why genomic printing has evolved in placental mammals is related to conflict.
Genomic imprinting in pregnancy
1. Silenced when inherited from either the father or the mother
2. Paternally expressed genes are expected to be associated with increased demands
on the mother, by offspring (IGF2)
3. Maternally expressed genes are expected to be associated with reduced demands on
the mother (IGf2R)
Genomic imprinting is one means of resolving conflict, one party switches of a gene, the
other party can set the valued trait to an optimum.
