Cell-Autonomous Immunity and The Pathogen-Mediated Evolution of Humans: Or How Our Prokaryotic and Single-Celled Origins Affect The Human Evolutionary Story

Host immune tactics at the level of the single cell have a very large effect on disease progression and host survival. These cell-level defense mechanisms, known as cell-autonomous immunity, are among the most important determinants of human survival, yet are millions to billions of years old, inherited from our prokaryotic and single-celled ancestors. An understanding of how cell-autonomous immunity has evolved in primates is crucial to understanding the human evolutionary story, not only because multiple infectious agents thought to have strongly affected human genomic evolution are excellent manipulators of cell-autonomous immunity, but because these defenses are found in every cell in every physiological system. The ubiquity of cell-autonomous immunity highlights a biological reality not commonly addressed in human evolutionary studies—that pathogens can mediate the evolution of all body cells and, therefore, all body systems, affecting human evolution in a cell-type-specific fashion. Here we explore these very ancient tactics in light of evolutionarily important human pathogens and illustrate inter-primate differences in the potential of such defenses. Often considered an independent physiological system in human evolutionary biology, the immune system is ubiquitous, integrated into every other aspect of human physiology. It is, effectively, the entire organism. We argue, therefore, that immunity and pathogen-mediated natural selection are considerations in the examination of the evolution and function of any human physiological system or trait.