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Title:   Author  item
                                            SU, CHUNLEI - University Of Tennesseeitem
                                            KHAN, ASIS - Washington Universityitem
                                            ZHOU, PENG - South China Agricultural Universityitem
                                            MAJUMDARA, DEBASHREE - University Of Tennesseeitem
                                            AJZENBERG, DANIEL - Hospital And University Center Of Limogesitem
                                            DARDE, MARIE-LAURE - Hospital And University Center Of Limogesitem
                                            ZHU, XINGQUAN - Washington Universityitem
                                            AJIOKA, JAMES - Cambridge Universityitem
                                            Rosenthal, Benjaminitem
                                            Dubey, Jitenderitem
                                            SIBLEY, L - Washington University
  Submitted to: Proceedings of the National Academy of Sciences (PNAS)
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/1/2012
                                    Publication  Date: 4/12/2012
                                    Citation: Su, C., Khan, A., Zhou, P., Majumdara, D., Ajzenberg, D., Darde, M., Zhu, X., Ajioka, J.W., Rosenthal, B.M., Dubey, J.P., Sibley, L.D. 2012. Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proceedings of the National Academy of Sciences. 5844-5849.Interpretive Summary: The variation among isolates of Toxoplasma gondii affects a wide range of important traits governing how this zoonotic parasite will be transmitted, and how severe the resulting veterinary or human disease may be.  Making progress into the basis of such variation requires a stable means to categorize isolates based on the evolutionary histories and genetic affinities.  Several distinct methods of genotyping have been employed to this end, but this manuscript reports the first attempt to combine these into a comprehensive, global analysis.  Nearly a thousand isolates were examined in this study, far more than earlier efforts have contemplated.  We found that only several ancestors likely contributed to the diversity present among parasites today; interestingly, parasites in North America and Europe generally represent outgrowths of a few, over-represented strains that spread asexually.  By contrast, variation elsewhere, especially in South America, is apportioned among myriad recombinant genotypes (none of which occurs with especially great frequency).  These data will serve as an important reference for future work, and will guide future efforts to pinpoint how heritable variation influences disease and transmission attributes.  The information will be of interest to epidemiologists, veterinarians, geneticists, and parasitologists.
                                Technical Abstract: Marked phenotypic variation characterizes isolates of Toxoplasma gondii, a ubiquitous zoonotic parasite that serves as an important experimental model for studying Apicomplexans.  Progress in identifying the heritable basis for clinically and epidemiologically significant differences require a stable system for describing and interpreting evolutionary subdivisions in this prevalent pathogen.  To do so, we have examined more than 950 isolates collected from around the world and genotyped them using three independent sets of polymorphic DNA markers, sampling 30 loci distributed across all nuclear chromosomes as well as the plastid genome.  Our studies reveal a biphasic pattern consisting of regions in the Northern Hemisphere where a few, highly clonal and abundant lineages predominate; elsewhere, and especially in portions of South America, frequent recombination engenders a diverse assemblages of rare genotypes.  Clustering methods were used to condense the marked genetic diversity of 138 unique genotypes into 15 haplotypes that collectively define six major clades.  Analysis of gene flow indicates that a small number of ancestral lineages gave rise to the existing diversity through a process of limited admixture.  Identification of reference strains for these major groups should facilitate future studies on comparative genomics and identification of genes that control important biological phenotypes including pathogenesis and transmission.


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