ABSTRACT
The relative influence of evolutionary forces, such as genetic drift or natural selection, on polymorphisms associated with altered susceptibility to pulmonary infection remains an open question.7 It should be borne in mind, however, that respiratory infection causes approximately 10 percent of deaths worldwide (and proportionately more historically).8 Thus, it seems likely that a selective advantage for some human polymorphisms may well have evolved, for reasons similar to the protection against Plasmodium falciparum-induced malaria that is afforded by hemoglobin S.9 For example, there has long been speculation (and corroboration in animal models) that the modern frequency of CFTR mutations in Caucasian populations came about as a result of heterozygous advantage against gastrointestinal infection.10-12 The case of Mycobacterium tuberculosis may prove to be particularly revealing in this regard, since this bacterium alone caused up to 25 percent of all deaths in Western Europe in the first half of the nineteenth century and has been a leading cause of early death from time immemorial.13 M. tuberculosis should be viewed as having as great a potential for polymorphism selection within certain human populations as malaria has had in other populations.14
