Digging Into Data The Cystic Fibrosis Mutation and Typhoid Fever The CF allele that causes most cases of cystic fibrosis is at least 50,000 years old and very common: 1 in 25 people carry it in some populations. Why is this allele so common if it is so dangerous? Consider that the CF allele is eventually lethal in homo zygous individuals, but not in those who are heterozygous. This allele is codominant with the normal allele. Heterozygous individuals typically have no symptoms of cystic fibrosis because their cells make enough of the normal CFTR protein to have normal chloride ion transport. Researchers think the CF allele has persisted because it offers heterozygous indi viduals an advantage in surviving certain deadly infectious diseases. The unmutated CFTR protein triggers endocytosis when it binds to bacteria. This process is an essen- tial part of the body’s immune response to bacteria in the respiratory tract. However, the same function of CFTR allows bacteria to enter cells of the gastrointestinal tract where they can be deadly. For example, internalization of Salmonella typhi bacteria by epithelial cells in the gut causes a common worldwide disease called typhoid fever. Symptoms include extreme fever and diarrhea, and the resulting dehydration causes delirium that may last several weeks. If untreated, it kills up to 30 percent of those infected. Around 600,000 people, most of whom are children, die from the disease each year. In 1998, Gerald Pier and his colleagues compared the uptake of S. typhi by different types of epithelial cells: those heterozygous for the CF allele, and those homozygous for the normal allele. (Cells homozygous for the CF allele do not take up any typhi bacteria.) Some of the results are shown in Figure 9.11 106 O Normal cells Cells heterozygous for the CF allele 10 10 Ty 2 167 7251 Strain of Salmonella typhi Figure 9.11 Effect of the CF mutation on uptake of three strains of Salmonella typhi bacteria by epithelial cells 1. Regarding the Ty2 strain of S. typhi, about how many more bacteria were able to enter normal cells (those expressing unmutated CFTR than cells expressing the gene with the CF mutation? 2. Which strain of bacteria entered normal epithelial cells most easily? 3. Entry of all three typhistrains into the heterozygous epithelial cells was inhibited. Is it possible to tell from this graph which strain was most inhibited?