Practice question

Sickle cell allele causes severe hemolytic disease in homozygous recessive state but confers malaria resistance in heterozygous condition in regions endemic for Plasmodium falciparum. Heterozygotes survive better than both AA individuals susceptible to malaria and SS patients with severe anemia, exemplifying overdominance with highest fitness in heterozygote. This balancing selection maintains S allele at frequency far higher than mutation alone would predict, despite strong purifying selection against SS. Heterozygote advantage therefore explains persistence of otherwise deleterious allele in African, Mediterranean, and Indian populations historically exposed.