BIOL 1004 Lecture Notes - Cystic Fibrosis, Zygosity, Allele Frequency

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30 Jan 2013
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(Pages 194 207)
6.3. Patterns of Selection: Testing Predictions of Population Genetic Theory
Selection on Recessive and Dominant Alleles
This chapter covers the mathematics behind the evolution of populations. Read the book
because I can’t explain numbers in words.
Chapter 6 (Pages 210 218)
6.4 Mutation
Adding Mutation to the Hardy Weinberg Analysis: Mutation as an Evolutionary Mechanism
Mutation by itself is generally not a rapid mechanism of evolution.
o For example in a population with a frequency of 0.9 for A alleles and a frequency of 0.1
for a alleles, a mutation rate of 1 per 10 000 (a high rate of mutation) would result in
frequency of 0.89991 for the A allele and frequency of 0.10009 for the a allele.
This number is very similar to the original frequencies of alleles within that given
Therefore, it would take 1000 generations for the allele frequency for A to
change from 0.9 to 0.81.
Mutation can cause substantial change in allele frequencies but it does slowly.
See Page 211 for clarification and the math shown
Mutation and Selection
It is not correct to assume that mutation is unimportant because of its unappreciable changes in
the allele frequencies of a population
Mutation combine with selection can become a crucial piece of the evolutionary process.
o Read experiment on page 212 and 213.
o The experiment shows that while mutation itself is only a weak mechanism of evolution,
it nonetheless supplies the raw material on which natural selection acts.
o Mutation is the ultimate source of genetic variation.
Mutation-Selection Balance
Most mutations are deleterious.
Selection acts to eliminate such mutations from populations.
Deleterious alleles persist, however, because they are continually created anew.
When the rate at which copies of a deleterious alleles are being eliminated by selection is
exactly equal to the rate at which new copies are beings created by mutation, the frequency of
the allele is at equilibrium mutation-selection balance.
What is the frequency of the deleterious allele at equilibrium?
o ^q = √(µ/s) *The ^ should be on top of the q.
o µ is the mutation rate and s is the selection coefficient (between 0 and 1) which
expresses the strength of selection against the allele.
o This equation tells about the mutation selection balance
If the selection coefficient is small (the allele is only mildly deleterious) and the
mutation rate is high, then the equilibrium frequency of the allele will be
relatively high.
If the selection coefficient is large (the allele is highly deleterious) and the
mutation rate is low, then the equilibrium frequency of the allele will be low
See Page 215 for mathematical work
Are the Alleles That Cause Cystic Fibrosis Maintained by a Balance between Mutation and Selection?
Cystic fibrosis is cause by recessive loss-of-function mutations in a locus on chromosome 7 that
encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR).
o CFTR is a cell surface protein expressed in the mucus membrane lining the intestines
and lungs
o One of its key functions is to destroy the Pseudomonas aeruginosa bacteria which cause
chronic lung infections in individuals with cystic fibrosis, leading to severe lung damage
Selection against the alleles that cause cystic fibrosis appear to be strong
o However, the alleles that cause cystic fibrosis have a collective frequency of
approximately 0.02 among people of European ancestry
Could cystic fibrosis alleles be maintained at frequency of 0.02 by mutation selection balance?
o If we assume a selection coefficient of 1 and use the equation derived in Box 6.10 (page
215), the mutation rate creating new disease alleles would have to be 4 x 10-4.
o The actual mutation rate for cystic fibrosis alleles appears to be considerably lower than
that: 6.7 x 10-7
o Thus a steady supply of new mutations cannot, by itself, explain the maintenance of
cystic fibrosis alleles at a frequency of 0.02..
There is another explanation to this situation which is based on heterozygote superiority
o The fitness cost suffered by cystic fibrosis alleles when they are in homozygotes is
balanced by a fitness advantage they enjoy when they are in heterozygotes.
o Read experiment on page 217 and 218 which employ this explanation.