by Michael A. Goldman, PhD, Professor and Former Chair, Biology, San Francisco State University
© 2022 by Michael A. Goldman
Infectious diseases have the power to rewrite the human genome. One of the most severe challenges we have faced in a century has come from SARS-CoV-2, the causative agent for COVID-19. The response of a host to a disease is partly controlled by genetic characteristics of the host, which vary from one individual to another. One genotype may result in a less severe disease than another. Differing outcomes for the disease can result from variations in susceptibility to the infection itself, in the innate immune response and its ability to control the infection at early stages, in the adaptive immune response and its ability to control the disease at later stages, and in the inflammatory response, which accounts for some of the most severe damage that the disease might cause. Further, different individuals may respond better to medical therapy than others, while other individuals may respond to vaccination with a greater or lesser degree of protection. All of these characteristics and the molecular interactions and the underlying genes that control them are subject to natural selection and evolution. However, differences in infection and outcome may also result from differential availability of medications, including vaccines, or lifestyle choices, such as the ability to isolate to avoid infection risk, attributable to socioeconomic reasons. These differences are not based on genetics and do not result in evolutionary alterations or adaptations to the pathogen.
One of the diseases that has had a very strong effect on human evolution is malaria, caused by various species of the parasite genus Plasmodium, including P. falciparum. Among the adaptations to malaria is heterozygosity for the sickle cell allele (Hb-S) coding for a mutant hemoglobin protein that (in homozygous condition) causes red blood cells to have a sickle shape. The heterozygous individuals are less subject to malaria infection, but the price they pay over generational time is the inevitable appearance of homozygotes for the sickle cell allele, who exhibit a severe anemia. The selective advantage conferred by the heterozygous state is called heterozygous advantage. The heterozygote is more resistant to malaria and is also only mildly affected or unaffected by the sickle cell trait, which can be fatal in the homozygous state. The result of this selective pressure is an unusually common disease allele because selection acts simultaneously against both the hemoglobin sickle cell allele (Hb-S) and the normal hemoglobin allele (Hb-A) when they are homozygous. In the absence of malaria, selection against Hb-S would cause the frequency of Hb-S to be much lower than is actually observed.