antigenic variation in plasmodium falciparum malaria involves a highly structured switching pattern恶性疟原虫疟疾抗原差异涉及到一个高度结构化的切换模式.pdfVIP

Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern 1 1,2 3 3 3 ´ Mario Recker *, Caroline O. Buckee , Andrew Serazin , Sue Kyes , Robert Pinches , Zoe 3 4 1 3 Christodoulou , Amy L. Springer , Sunetra Gupta , Chris I. Newbold * 1 Department of Zoology, University of Oxford, Oxford, United Kingdom, 2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, 4 Department of Biology, Amherst College, Amherst, Massachusetts, United States of America Abstract Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise