title: Escape from bacterial iron piracy through rapid evolution of transferrin.
abstract: Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Barber
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. nelde@genetics.utah.edu.
authors.forename: Nels C
authors.initials: NC
authors.lastname: Elde
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019143:Evolution, Molecular; D006193:Haemophilus influenzae / Q000378:metabolism*; D000882:Haplorhini / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009343:Neisseria / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000378:metabolism; D009345:Neisseria meningitidis / Q000378:metabolism; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011485:Protein Binding; D012641:Selection, Genetic; D014168:Transferrin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D033881:Transferrin-Binding Protein A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014168:Transferrin; D033881:Transferrin-Binding Protein A