Sample problem illustrating the use of
Population Genetics Simulation and Tutorial
Cystic fibrosis alleles and mutation-selection balance
Cystic fibrosis is caused by recessive mutations (A -> a) in a locus
on chromosome 7 that encodes a protein called the cystic fibrosis
transmembrane conductance regulator (CFTR). Pier et al (1997)
suggested that one of the CFTR's key functions is to enable cells of
the lung lining to ingest and destroy Pseudomonas bacteria,
thereby protecting the lung. Individuals with cystic fibrosis (aa) are
less protected and these bacteria can result in chronic lung
infections, leading to severe lung damage, and until recently, few
affected individuals survived to reproductive age. The allele
frequency is approximately 0.02 among people of European
ancestry, and the measured mutation rate creating new alleles is
0.00000067, which is too low to maintain this high a frequency.
Pier et al (1997) indicate that reduced CFTR protein in cystic
fibrosis heterozygotes (Aa) may make it harder for Salmonella
typhi bacteria to cross the epithelial cells lining the gut, thereby
making them more resistant to typhoid fever.
If the fitness of 'aa' is zero, and the measured mutation rate is valid,
what selection against 'AA' would be needed to maintain the 'a'
allele at its frequency of 0.02? (run simulations for 500 generations)
Pier, G. B., M. Grount, and T. S. Zaidi. 1997. Cystic fibrosis tansmembrane
conductance regulator in an epithelial cell receptor for clearance of
Pseudomonas aeruginosa from the lung. Proceedings of the National
Academy of Science 94:12088-12093.