Lecture 11: Random mating and The Hardy-Weinberg Principle

The Hardy-Weinberg principle Define evolution again

Evolution is testable and predictive. Theory (such

Today’s topics: as the Hardy-Weinberg Principle) predicts how
1. The Hardy-Weinberg Principle evolution should occur.
2. Does a gene pool have H-W frequencies?
3. Example: HWE test
4. Example: Cystic fibrosis

Readings: Pierce: 337-341

The Hardy-Weinberg Principle The Hardy-Weinberg Model

1908: proposed by G.H. Hardy and W. Weinberg
Hardy-Weinberg Law
Under model assumptions, a gene pool will have
1) constant allele frequencies over time
2) predictable genotype frequencies (= p2, 2pq, q2 for 2
alleles)
The H-W Law works because of the nature of sexual
reproduction:
1. Model for one population, alleles A and a.
p = f(A), q = f(a).
Very often, p is for dominant allele, q for recessive.

The H-W Equilibrium

If the gene pool meets these two predictions, it is at
equilibrium, and no evolution occurs.
 The Hardy-Weinberg Model The Hardy-Weinberg Model
f(A) and f(a) in jars full of gametes should be … ?
1. p = f(A), q = f(a)
Answer: p and q in each
2. Gametes from males and females are put into separate
“jars” (gamete pools).
p, q p, q
sperm gamete egg gamete
pool pool

sperm egg gamete

gamete pool pool
p, q "gamete pool"
Assume that every male makes many sperm and every female
makes many eggs.
Since the math is the same, we consider only one "gamete
Effectively, an infinite gamete pool. this is why we can
summarize with frequencies. BUT not infinite number of pool", without keeping track of eggs and sperm separately.
individuals

The Hardy-Weinberg Model Random Mating Frequencies

A?
3. Gametes picked at random to form zygotes that
represent the next generation. gamete pool A?

we are ignoring
the actual mating Genotype frequencies in the next generation
event, and using
statistics to
summarize many
independent
f(AA) = f(A-sperm) x f(A-ovum)
gamete pool remember the "AND" rule
mating events
p, q
= p x p = p2
f(aa) = f(a-sperm) x f(a-ovum)
(All adults die.) = q x q = q2
4. Calculate genotypic frequencies for the next f(Aa) =[f(A-sperm) x f(a-ovum)]
generation. + [f(a-sperm) x f(A-ovum)]
Allele frequencies are also probabilities of picking = (p x q) + (q x p) = 2pq
an allele, if mating is random.
 Random Mating Frequencies The Hardy-Weinberg Principle

Random mating frequencies can also be viewed as a Important points

Punnett Square.
1. Allele frequencies now exactly determine genotypic
sperm pool frequencies in the next generation.
A a
They follow the binomial expansion:
A p2 pq (p + q)2 = 1
p2 + 2pq + q2 = 1
egg
pool
a qp q2

See Figure 12.2 in the text.

The Hardy-Weinberg Principle The Hardy-Weinberg Principle

2. Allele frequencies in the next generation (p' and q') are 3. With random mating, allele frequencies will ALWAYS be
identical to those now (p and q): p and q and genotype frequencies will ALWAYS be p 2 ,
2pq, and q 2 .
p' = 2p 2 + 2pq aa
Aa
p and q
2 AA AA A population with these frequencies that does not change
… over time is in "H-W equilibrium".
p' = p p and q
p and q

gamete pool p and q

Aa
AA AA p and q
p' and q'
...
Does a gene pool have H-W frequencies? Example: H-W equilibrium test
(Observed - Expected)2
4. A gene pool with p2, 2pq, q2 has H-W frequencies.
χ2 = Σ Expected

Statistically compare expected H-W genotype An example:

frequencies to observed genotype frequencies with AA Aa aa Total
a chi-square goodness-of-fit test: Obs. # 75 34 60 169
Obs. freq. 0.444 0.201 0.355 1.000
(# Observed - # Expected)2 p = 0.544 and q = 0.456
χ2 = Σ # Expected
Exp. freq. p2 2pq q2
0.296 0.496 0.208 1.000
Exp. # 50.0 83.8 35.2 169

Is a gene pool in H-W equilibrium? More on Hardy Weinberg …

1. Random mating gives the "H-W frequencies" p2,
AA Aa aa Total 2pq, q2 in the zygotes even if p and q are changing
(#O - #E) 25.0 -49.8 24.8 over time.
… → p2, 2pq, q2 will be seen in the offspring from random mating,
(#O - #E)2/#E 12.5 29.6 17.5 59.6 even if the population is not in "H-W equilibrium".
→ call p 2, 2pq, q 2 the "random mating frequencies"
χ2 = Σ (#O - #E)2/#E = 12.5 + 29.6 + 17.5 = 59.6
χ2 = 59.6, d.f. = 1, p = 0.0001 (from a stats table) 2. H-W law applies to any number of alleles.
For p < 0.05, the critical χ2 value for 1 d.f. is 3.84 e.g., random mating frequencies for 3 alleles:
should know this from Bio 215 !!! p+q+r=1
Conclusion: (p + q + r)2 = 1
This population does NOT have H-W frequencies! p2 + 2pq + 2pr + q2 + 2qr + r2 = 1
 More on Hardy Weinberg … More on Hardy Weinberg …
2. H-W law applies to any number of alleles.
e.g., random mating frequencies for 3 alleles: 3. p = 0 or q = 0 does not depart from HW
p+q+r=1 expectations
(p + q + r)2 = 1 See Table 12.1
4. By assuming H-W equilibrium or random
p2 + 2pq + 2pr + q2 + 2qr + r2 = 1
mating, the genotype frequencies can be
normally, don't know the heterozygotes
He = expected heterozygosity = 2pq + 2pr + … estimated from very little information.
= 1 - Σ (p2 + q2 + r2 + …)
Easier formula for 3+ alleles
(see also eq. 5.1 in Stearns)

Ho = observed frequency of (See notes from

heterozygotes in the sample last lecture.)

Example: Cystic Fibrosis Cystic Fibrosis

some people say "assuming HWE"

Rare disease caused by a recessive allele If random mating is ASSUMED, then:

q2 = 0.0006
Observation: 1 in 1667 (= 0.0006) people has cystic
fibrosis. q = √ q2 = √ 0 .0006 = 0.0245
p = 1 - q = 0.9755
What can we say about the C.F. gene pool? 2pq = 2(0.9755)(0.0245) = 0.0478
-> Heterozygote carriers do not have the
disease
disease of the pancreas and lungs. Conclusion: 1 in 1667 persons has cystic fibrosis, but
Caused by mutations in a membrane chloride nearly 1 in 20 carries the allele!
channel. Most common mutation is a 3 bp
deletion
 Cystic Fibrosis H-W summary

Lesson: Rare recessive alleles exist primarily in 1. H-W equilibrium is ONLY found with:
heterozygotes. -- in this example there are 80X as many of
the alleles in heterozygotes as in
homozygotes. show with M&Ms
a. random mating
Note that since we are assuming the population has b. large population size (no genetic drift)
HW frequencies, we cannot do a χ2 test here! c. no mutation
(Can only do χ2 when the # heterozygotes is actually d. no migration
known.) e. no natural selection

The 5 "evolutionary forces"

To get HW frequencies in zygotes, only assumption
1 may be needed

H-W summary

2. This is the most basic model in population

genetics.
Departures from H-W frequencies imply that
Next Time:
other evolutionary forces may be acting. Nonrandom Mating
See last paragraph on p. 341.