Human Heredity 10th Edition by Michael Cummings

Exercise 2

Natural selection alters genotypic frequencies by increasing or decreasing fitness (i.e., differential fertility or mortality). There are several examples of selection associated with human genetic disorders. Sickle cell anemia and other abnormal hemoglobins are the best examples of selection in humans. Carriers of the sickle and other hemoglobin mutations are more resistant to malaria than is either homozygous class. Therefore, in areas where malaria is endemic, carriers are less likely to die of malaria and will have proportionally more offspring than will homozygotes, thus passing on more genes. Balancing selection may also have influenced carrier frequencies for more "common" recessive diseases, such as cystic fibrosis in Europeans and Tay-Sachs in the Ashkenazi Jewish population, but the selective agent is not known for certain.
Selection may favor homozygotes over heterozygotes, resulting in an unstable polymorphism. One example is selection against heterozygous fetuses when an Rh mother carries an Rh1 (heterozygous) fetus. This should result in a gradual elimination of the Rh allele. However, the high frequency of the Rh allele in so many populations suggests that other, unknown factors may maintain the Rh allele in human populations.
If allele frequencies in the hemoglobin gene are influenced by sickle cell anemia on the one hand and by resistance to malaria on the other hand, what factors may cause a change in these allele frequencies over time