Ancient microbial arms race sharpened our immune system—but also left us vulnerable
(Science) At a recent symposium on the evolution of infectious diseases, University of California, San Diego (UCSD), pathologist Nissi Varki noted that humans suffer from a long list of deadly diseases—including typhoid fever, cholera, mumps, whooping cough, measles, smallpox, polio, and gonorrhea—that don’t afflict apes and most other mammals. All of those pathogens follow the same well-trodden pathway to break into our cells: They manipulate sugar molecules called sialic acids. Hundreds of millions of these sugars stud the outer surface of every cell in the human body—and the sialic acids in humans are different from those in apes.
Varki and an international team of researchers have now traced how evolution may have scrambled to construct new defenses after that molecular vulnerability emerged in our distant ancestors. By analyzing modern human genomes and ancient DNA from our extinct cousins, the Neanderthals and Denisovans, the researchers detected a burst of evolution in our immune cells that occurred in an ancestor of all three types of human by at least 600,000 years ago.
As the researchers report in the current issue of Genome Biology and Evolution, these genetic changes may have sharpened the body’s defenses against the pathogens that evolved to exploit sialic acids—but created new vulnerabilities. In an added irony, they note, humans’ distinctive sialic acids were themselves once a defense against disease. The evolutionary saga is a vivid illustration of the competition between humans and microbes, says microbiologist Christine Szymanski of the University of Georgia, Athens, who is not a co-author. “This gives us a human perspective on how we have to keep changing to keep pace.”
The arena for this evolutionary arms race is the glycocalyx, a sugar coating that protects the outer membrane of all cells. It consists of a forest of molecules that sprout from the cell membrane. The sialic acids are at the tip of the tallest branches, sugar chains called glycans, which are rooted to fats and proteins deeper in the membrane.
The influenza A virus, shown in a stylized scanning electron microscopic image, is one of many pathogens that take advantage of a 2-million-year-old evolutionary change in the surface of the human cell in order to slip inside it.