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Human DNA Shows Traces of 40 Million-Year Battle For Survival Between Primate and Pathogen over Iron in Bloodstream

Stashed in: Primates!, Awesome, Medicine, Science Too, The Nature of the Beast, Evolution, Microbiome, DNA

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Bacteria want our iron! Isn't it ironic?

Examination of DNA from 21 primate species – from squirrel monkeys to humans – exposes an evolutionary war against infectious bacteria over iron that circulates in the bloodstream. Supported by experimental evidence, these findings, published in Science on Dec. 12, demonstrate the vital importance of an underappreciated defense mechanism, nutritional immunity. 

“We’ve known about nutritional immunity for 40 years,” says Matthew Barber, Ph.D., first author and postdoctoral fellow in human genetics at the University of Utah. “What this study shows us is that over the last 40 million years of primate evolution, this battle for iron between bacteria and primates has been a determining factor in our survival as a species.”

The study models an approach for uncovering reservoirs of genetic resistance to bacterial infections, knowledge that could be used to confront antibiotic resistance and emerging diseases.Following infection, the familiar sneezing, runny nose, and inflammation are all part of the immune system’s attempts to rid the body of hostile invaders. Lesser known is a separate defense against invasive microbes, called nutritional immunity, that quietly takes place under our skin. This defense mechanism starves infectious bacteria by hiding circulating iron, an essential nutrient it needs for survival. The protein that transports iron in the blood, transferrin, tucks the trace metal safely out of reach. 

Clever as it sounds, the ploy is not enough to keep invaders at bay. Several bacterial pathogens - including those that cause meningitis, gonorrhea, and sepsis - have developed a weapon, transferrin binding protein (TbpA), that latches onto transferrin and steal its iron. Though scientists have known of the offensive strategy, they failed to realize how pivotal the battle over iron has been in the conflict between host and pathogen.

Best Reddit comment:

This paper was really interesting. It basically says that our bodies have to hide nutrition in proteins to keep that nutrition from being used by invaders and pathogens. They refer to this idea as, "nutritional immunity." For iron, we have to do this through a protein shell called, transferrin. The protein does a good job of protecting the iron, but it has a weak spot that many invaders who need iron have discovered. There is an area on this protein that the pirate invaders can dock onto. This docking area has been continuously renovated by our DNA code to try to make it less hospitable. In return, the invaders have added new proteins that allow them to dock to the changed landing site. About 25% of humans carry a docking station that is very inhospitable to many pathogens. This understanding of the war between docking station and docking gear could very much lead to new classes of antibiotics.

400 Reddit comments:

Every day I'm Transferin ...

Transferin iron vesicle transport harvard

Even the words "vesicle transport" are thrilling.

As is the term "nutritional immunity".

I wish there were such a thing as "caloric immunity".

We can dream, Geege.