title: An evolutionary perspective of how infection drives human genome diversity: the case of malaria.
abstract: Infection with malaria parasites has imposed a strong selective pressure on the human genome, promoting the convergent evolution of a diverse range of genetic adaptations, many of which are harboured by the red blood cell, which hosts the pathogenic stage of the Plasmodium life cycle. Recent genome-wide and multi-centre association studies of severe malaria have consistently identified ATP2B4, encoding the major Ca(2+) pump of erythrocytes, as a novel resistance locus. Evidence is also accumulating that interaction occurs among resistance loci, the most recent example being negative epistasis among alpha-thalassemia and haptoglobin type 2. Finally, studies on the effect of haemoglobin S and C on parasite transmission to mosquitoes have suggested that protective variants could increase in frequency enhancing parasite fitness.
authors.affiliation: Department of Public Health and Infectious Diseases, University of Rome 'La Sapienza', Rome, Italy; Istituto Pasteur, Fondazione Cenci Bolognetti, University of Rome 'La Sapienza', Rome, Italy. Electronic address: valentina.mangano@uniroma1.it.
authors.forename: Valentina D
authors.initials: VD
authors.lastname: Mangano
authors.affiliation: Department of Public Health and Infectious Diseases, University of Rome 'La Sapienza', Rome, Italy; Istituto Pasteur, Fondazione Cenci Bolognetti, University of Rome 'La Sapienza', Rome, Italy. Electronic address: david.modiano@uniroma1.it.
authors.forename: David
authors.initials: D
authors.lastname: Modiano
mesh_terms: D000222:Adaptation, Physiological; D000483:Alleles; D000818:Animals; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008288:Malaria / Q000453:epidemiology / Q000235:genetics* / Q000469:parasitology; D010961:Plasmodium