(ii) The fact that the gene frequency—like that of hemoglobin S in Africa—is high argues for a high mortality from malaria in Papua New Guinea. Although high mortality is not seen today because of chloroquine, it may be a problem in the future when antimalarial drugs become ineffective. (iii) Why have band 3 mutations in Papua New Guinea never occurred in Africa, and why has hemoglobin S never occurred in Papua New Guinea? Other erythrocyte skeletal mutations have been identified in Africa that appear to affect parasite development (5, 6). (iv) Despite the slow evolution of the human genome compared to that of the parasite, the host innate resistance mechanisms can afford improved survival. It may not be in the best interest of the parasite to kill its host.

The fact that certain polymorphisms such as hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency were selected for by malaria is well known (7, 8). I am going to explore other genetic differences that exist between Africans and Caucasians that may have been selected for by malaria and what clues they may provide for drug and vaccine development. Some of these polymorphisms are deleterious; genetic markers for these would identify individuals at risk for preventive therapy. Others are neutral as far as we know and have gone to fixation at 100%.

HYPERTENSION AND IRON OVERLOAD

Hypertension and liver disease are two major diseases that affect African Americans at a higher frequency than European Americans. Because the genetic bases are unknown, the potential that these genes confer resistance to malaria should be considered.

There are many hypotheses for the selective force that led to the increased incidence of hypertension in African Americans. Theories postulate that African Americans, who retain salt more avidly than European Americans, were selected for because of limited availability of salt in Africa, death during the transportation of slaves from Africa to America, or death during subsequent life as a slave in America. The validity of these hypotheses has been questioned by historian Philip Curtin (9). He pointed out that most slaves lived within 100 miles of the African coast where there was a readily available, inexpensive source of salt from evaporation of sea water. He also examined the causes of death in slaves and found no evidence for an excess of diseases related to salt loss.

I would like to raise the possibility that differences in salt metabolism, especially as they may be reflected in erythrocytes, may have been selected by malaria. The erythrocytes of African Americans are known



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