This case was put forth many years ago for sickle cell anemia, in which it was observed that heterozygotes for the sickle cell allele were more resistant to malaria. In fact, sickle cell anemia among Africans is most prevalent in those regions where malaria is also prevalent. In the heterozygous state, where individuals have a partial dose of sickle cells, along with normal cells, blood cells are less susceptible to invasion by the protozoan parasite that causes malaria. Thus, during historical times, there was an advantage to being a carrier of the sickle cell allele, even to the extent that heterozygotes survived more frequently than homozygous individuals with the normal allele. This new theory posits that in the days of Stone Age hunters and beyond, cholera was one of the most frequent causes of death.
Cholera causes intense diarrhea and dehydration, which if untreated often causes death.
Individuals that were heterozygous for the cystic fibrosis allele may have been less susceptible to cholera because a single dose of the gene may have caused some tendency for thickened mucus in the intestinal tract and better water retention during bouts of cholera and other intestinal diseases. Also recently, a theory has emerged that there has been a selective advantage within Eastern European Jews for the Tay Sachs allele in the heterozygous state. Tuberculosis was a major killer in the urban ghettos of eastern Europe during the past few centuries. Eastern European Jews, because of past persecution, were often forced to live in such ghettos, and died frequently of tuberculosis. Non-Jews in this region often emigrated to rural settings where tuberculosis was less prevalent.