Genetics. The battle for iron.


SCIENCE I nfections exert selection pressures on host and pathogen alike as they both struggle to survive. Host genes important for the immune response to infection often show enhanced rates of diversification, termed positive selection, between and even within species ( 1, 2). Sequence analysis can reveal “hotspots” in proteins that have been selected by evolution and are critical to repel infections. For example, proteins that recognize viruses exhibit amino acid diversity in the specific regions that directly contact components of the virus ( 1). Of course, viruses can and do counteradapt through selection of variants that evade recognition by defense proteins ( 1). Bacterial infections are also likely to positively select mammalian genes important for immune defense. On page 1362 of this issue, Barber and Elde ( 3) provide one striking example of this that is centered on iron. Why iron? Humans need it to grow, but so do almost all organisms that infect us, because it supports basic cellular processes such as electron transport and DNA metabolism. The virulence of infectious organisms is often highly dependent on their ability to assimilate host iron ( 4). However, the host fights back: Upon detection of infection, the innate immune system interfaces with the circuitry that controls iron transport. Increased synthesis of several ironand heme-binding proteins and of the iron regulatory hormone hepcidin ( 5) lowers serum iron availability for blood-borne pathogens. Another key component of mammalian iron transport is the serum protein transferrin, and it is this protein that Barber and Elde focus on. Transferrin has two lobes, N and C, each of which binds one ferric ion (see the figure). Transferrin receptors at the cell surface enable cellular iron uptake. The extremely high affinity of transferrin for iron efficiently withholds iron from many pathogens. Indeed, when Schade and Caroline reported the purification of transferrin in 1946 they The battle for iron

DOI: 10.1126/science.aaa2468

Cite this paper

@article{Armitage2014GeneticsTB, title={Genetics. The battle for iron.}, author={Andrew E. Armitage and Hal Drakesmith}, journal={Science}, year={2014}, volume={346 6215}, pages={1299-300} }