- 9:3:4 tells epistatic interaction between these 2 genes

- We’re going to be concerned with the genotype and allele frequencies in a

population, how those genotype and allele frequencies change over time
- On right principally 4 forces → when talking about evolutionary biology → we’re talking
about 4 things that can happen to change allele frequencies/change genotype frequencies in a
population → in other words, cause evolutionary change
- Mutation is quite a slow process
- migration from one population to another can change allele and genotype
frequencies if the 2 populations differ in them
- natural selection causing selective change in genetic composition of population
overtime
- in very small populations there is a directionless force (does not have a direction) but can
change allele frequencies and genotype frequencies in random manner → called genetic drift

- Which are the predominant forces? Still an unresolved question in general

- Left is frequency of B blood type for humans across all of europe
- Can see frequency of B blood type is relatively low in places like Spain and Portugal and then
rises up in those other areas → why is that? He’s not going to answer it but this is the kind of
question that population geneticists is trying to deal with
- Right is another example of type of question population geneticists might be looking at →
this is allele frequency change overtime of 50 generations in population of fruit flies (only
looking at the 1 gene, Adh)
- These are just examples of the types of questions you encounter in population
genetics
- One other example is the frequency of sickle cell anemia → disease concentrated in
equatorial regions of the world
- If have 1 copy of this allele and WT copy of other allele (good copy) → have advantage in
equatorial regions of the world because when you’re heterozygous for this mutation → turns
out you have an advantage in the presence of malaria parasite → when parasite encounters a
heterozygous genotype it cannot proliferate as easily → homozygous for the normal WT
allele is actually at a disadvantage
- This can help explain why you find a high frequency of this mutation in equatorial
regions
- More and more geneticists find themselves dealing with sequence data (since so
cheap nowadays)
- Here have sample of 7 individuals and each of those lines is a diff sequence from diff
individual (top line is 35 base pair positions) → can see variation here
- Ex: can see at base pair position number 2 there are some segregation on G and C
nucleotide
- If look across can see there are quite a few nucleotide positions that differ between
these individuals, there are also indels where some individuals (5 and 6) some
portion of the sequence, there is also microsatellite which is a repeat (AGAGAG) and
can see there is variation in the number of AGAG repeats between individuals
- Haplotype variation is another type of variation → a somewhat arbitrary term, we’re
restricting definition to base pairs 1-35 on chromosome 22 for example and we are looking at
entire sequence across the 35 base pairs → not all individuals have same identical 35 base
pairs in a row (there is variation) → we talk about that as haplotype variation

- Answer: 3 haplotypes
- Only 3 entire sequences that are unique, rest of individuals share those sequences
- Answer: 2
- SNP is a variant
- 2 positions that are varying in these haplotypes (position 1 and 11 varies depending
on which individual you are looking at)
- Haplotypes tell us something often about population histories
- Can see history of migration

- SNP: single nucleotide polymorphisms

- 1. When he says frequencies of alleles actually includes things such as SNPs
- 3. Population genetics is very theory heavy part of genetics → it uses models to try to make
predictions about allele frequency change overtime etc.

- First model he’s introducing is abstract way to think about populations

- This model has population with some boundary around it, focus in on what’s happening
within that boundary → can go into boundary and count up number of the individuals with
each of the diff genotypes that a single locus for example at A locus
- Can also count up number of alleles of each type → 18A and 14a alleles
- This kind of population doesn’t really exist in nature but close enough to the truth
where we can use this approach to give genotype frequencies and allele frequencies
in a hypothetical population
- Going to work with frequencies, so want to convert these numbers to frequencies by
dividing their respective totals
- There are 16 genotypes there, if divide by 5, 8, and 3 → come up with genotype freuqnecies
for these diff genotypes
- Have 32 alleles total → if divide by 18, 14 → have allele frequencies
- Standard notation
- Have notation for the frequencies of the genotypes → F with subscript for the genotypes
- If talking about all the genotypes in the population → their frequencies have to sum to 1
- Little p and little q for frequency of big A and little A respectively → they also have to sum to
1
- Useful to remember this equation → if know frequency of one of these alleles at dialocus that
has 2 alleles → you know the frequency of the other because they have to sum to 1
- Example of codominance is found in the blood type with M and N as the 2 alleles
underlying the phenotype
- These code for antigens on surface of RBC
- If homozygote for big M → have M blood type, if heterzygote → have antigens for both
(codominance) etc. → useful for population geneticists because simply by counting up
phenotypes, can determine the genotype frequencies in the population
- Here would interact the blood with antibody → see a reaction (ex: see an Anti-M reaction but
not anti-N reaction in the case of the M blood type, see both in the case of the heterzygote
etc.)
- Can go directly from phenotype to genotype and count up number of individuals from the
population who have each of these → determine the genotype frequencies
- Remember not every phenotype will allow you to do this, if there’s dominance you’re out of
luck → will have to use another approach
- If you get these frequencies → can easily calculate the underlying allele freuqnecies
- Can go from genotype frequencies to allele frequencies by taking frequency of homozygote
and half the frequency of heterzygote (makes sense since it does not have 2 copies of the M
allele so have to take half of those when converting genotype to allele frequencies) → give
for the M allele the frequency p is equal to 0.89
- Can also do 1-p to get the same 0.11 answer
- Answer: yes and no → need to know something else about the population → Hardy weinberg
theory

- Same question as last slide

- This is the answer → getting at the assumptions of the Hardey-Weingburg theory
- If have random mating means there is no tendency in this example for big A, big A
genotypes to mate with big A, big A genotypes more often than chance alone with big
A (can rewatch if don’t understand)
- No selection acting at this locus → no advantage to being any of these genotypes in terms of
reproduction and survival
- No migration or drift → the population is assumed to be very large so small population
effects don’t come into play and no migration back and forth between 2 populations

- In many cases populations are very close to behaving this way that Hardy-Weinburg
principle is useful to us
- Rate of mutations is slow, not going to greatly affect frequency change if just looking
at relatively short period of time
- Many genotypes are selectively neutral → no real advantage to being 1 genotype or another
- Migration → many populations are isolated enough from other populations such that
migration rate is relatively low
- If population is large enough → the affects of genetic drift on changing the allele frequency
by chance alone is relatively minor
- So although these assumptions seem restrictive → not necessarily completely restrictive so
can use Hardy-Weinburg to make some predictions about populations
- When those assumptions hold, can represent the genotype frequencies in the next
gen in form of punnet square
- Think of Eggs and sperm each with their individual A or little A alleles
- If have random mating, no mutation, no selection, no drift → p’s and q’s going to remain the
same in current and next generation
- When combine them in random fashion → come up with these proportions (p squared, 2pq, q
squared) → these are the Hardy-Weinburg proportions
- If Hardy Weinberg conditions hold (if the population hold generation after generation) →
once the population is in this configuration of P squared, 2pq, q squared → it’s just going to
remain there
- So we’d actually only take a single generation that the population is currently not in those
proportions that has some other genotype frequencies besides P squared, 2pq and q squared
→ a single generation of Hardy Weinberg conditions will drive the population into these
proportions
- And as long as those hardy weinburg conditions continue to hold, the population will
remain in those proportions

- This is our simple gene pool model overlaid with a few assumptions → turns out to be a
useful abstraction
- Answer is yes but only when Hardy Weinburg conditions hold

- Up on top is genotypes and some observed frequencies

- Answer: D
- First step to look at allele frequencies in the population which you have to calculate from the
genotype frequencies → find p=0.3, q=0.7
- Then do predicted Hardy-Weinburg p squared, 2pq and q squared
- Remember predicted Hardy-Weinburg frequencies only hold when those
assumptions are present in a population
- Looking at locus with 3 alleles, more than 1 heterozygote
- Answer: B

- If take those genotype frequency at face value and use the logic shown in yellow box →
homozygote plus half of relevant heterzygote → will come up with allele frequencies
- He is going to convince us that Hardy Weinburg is useful in real life
- CF is recessive so may be some carriers in this population of CF allele
- Suppose we don’t know the frequency of carriers in the population but we do know
the number of individuals in a population that are showing the disease
- He answers in next lec