For millennia, pathogens and human hosts have engaged in a perpetual struggle for supremacy. From the earliest recorded smallpox epidemics around 1350 B.C.E to the Black Death due to Yersinia pestis in the Middle Ages and continuing to modern times with HIV, there has been a continuous clash between pathogens and human hosts. But past pandemics are more than just ancient history—they are drivers of human genetic diversity and natural selection. Pathogens can dramatically decrease survival and reproductive potential, leading to selection for resistance alleles and elimination of susceptibility alleles. Despite this persistent struggle between host and pathogen, only in the past century have we developed an understanding of some of the human genetic differences that regulate infectious disease susceptibility and severity.
Studies identifying and characterizing alleles associated with infectious diseases from around the world have led to a better understanding of how the history of past pandemics is written in our genomes. The selective force of infectious diseases has had lasting impacts on our genetic susceptibility to ancient and emerging infections as well as autoimmune and chronic diseases. This story is ongoing and changes will continue to be written into our genomes by new and future infectious diseases.