Non-Expert Post: Biology: Human DNA Shows 40 MY Battle between Primate and Pathogen

I am an astronomer, and have spent vast amount of my time studying Space and Astronomy, and even a bit of Planetary Geology.  As a Science communicator and someone interested in how the world works, all types of Science fascinate me, and sometimes stories pop up that are really interesting to me.  It also helps that the current exhibit at the Ontario Science Centre is about the Brain.  This has me spending a lot of time learning how the Brain works and how it has evolved over the generations that led to our current human brains and bodies.

So in the spirit of broadening my horizons, I want to introduce an occasional non-expert post.  The disclaimer in all this is that I am looking at the story from the eyes of an enthusiastic observer, and so I won’t be able to fill in the gaps of the Science in the way I try to do with Astronomy.  So let’s learn together. Today: The resilience of Humanity revealed in a 40 Million year evolutionary battle between primates and the deadly pathogens that we have resisted over time.

We all get sick, in fact I’ve been sick far too often this fall, and one of the results of infection is the well known immune response.  We get a runny nose, sneeze, cough, fever, fatigue, inflammation, and a host of other symptoms that are all a response to hostile invaders in the body.  We also have a lesser known immune response, called nutritional immunity, that takes place below the skin where we barely notice it.  It involves the body starving pathogens of Iron, which they need for survival, by hiding it inside the protein transferrin, which transports Iron in the bloodstream.

Still, Evolution doesn’t choose favourites.  Bacteria have evolved a protein called Transferrin Binding Protein (TbpA) that can liberate the Iron from the transferrin.  Though we have known of this attack mechanism for a long time, we never realized its importance in the fight for survival.

A recent study of the DNA of 21 primate species from Monkeys to Humans has shown just how important nutritional immunity is. The study shows how the battle for Iron over the past 40 Million years has led to the evolution of our nutritional immunity, and has defined our resistance to foreign invaders.

Traces of the Pathogen battle seen in Human DNA worldwide. Source: University of Utah Health Care

“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.”

Interactions between the proteins are temporary, but their evolution catalogues the battle.  By looking at transferrin and TbpA over time, they could see the battle unfold as small changes occurred over the area where they interact, going back and forth between the liberation and protection of Iron.

The most recent sign of this long battle is a small mutation in the transferrin gene, which prevents recognition by infectious bacteria. “Up until this study no one had come up with a functional explanation for why this variation occurs at an appreciable frequency in human populations,” says senior author Nels Elde, Ph.D., assistant professor of human genetics at the University of Utah. “We now know that it is a consequence of the pathogens we and our ancestors faced over millions of years.”

The importance of this study is in finding new ways to resist pathogen invasion as we find new emerging diseases and antibiotic-resistant bacteria.

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The above video shows how transferrin (Green) and TbpA (Blue) have evolved (dots) along the contact site to battle between protection of Iron by transferrin and liberation of Iron by TbpA.

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