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Title: Comparative genomic sequence variation of Toxoplasma gondii reveals local admixture drives concerted expansion and diversification of secreted pathogenesis determinants

Author
item LORENZI, H - J Craig Venter Institute
item KHAN, A - Washington University School Of Medicine
item BEHNKE, M - Washington University School Of Medicine
item LIU, L - University Of Georgia
item NAMASIVAYAM, S - University Of Georgia
item SESHADRI, S - Hospital For Sick Children (SICKKIDS)
item HADJITHOMAS, M - J Craig Venter Institute
item KARAMYCHEVA, S - J Craig Venter Institute
item PINNEY, D - University Of Pennsylvania
item BRUNK, B - University Of Pennsylvania
item AJIOKA, J - Cambridge Institute Of Medical Research
item AZJENBERG, D - Hospital And University Center Of Limoges
item BOOTHROYD, J - Stanford University
item BOYLE, J - University Of Pittsburgh
item DARDE, M - Hospital And University Center Of Limoges
item Dubey, Jitender
item GRIGG, M - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)
item HOWE, D - University Of Kentucky
item KIM, KAMI - Albert Einstein College Of Medicine
item Rosenthal, Benjamin
item SAEIJ, J - Massachusetts Institute Of Technology
item SU, C - University Of Tennessee
item WHITE, M - University Of San Francisco
item ZHU, X - Chinese Academy Of Agricultural Sciences
item PARKINSON, J - Hospital For Sick Children (SICKKIDS)
item KISSINGER, J - University Of Georgia
item ROOS, D - University Of Pennsylvania
item SIBLEY, L - Washington University School Of Medicine

Submitted to: Nature Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2015
Publication Date: 1/7/2016
Citation: Lorenzi, H., Khan, A., Behnke, M.S., Liu, L., Namasivayam, S., Seshadri, S., Hadjithomas, M., Karamycheva, S., Pinney, D., Brunk, B., Ajioka, J., Azjenberg, D., Boothroyd, J.C., Boyle, J., Darde, M.L., Dubey, J.P., Grigg, M., Howe, D., Kim, K., Rosenthal, B.M., Saeij, J., Su, C.L., White, M., Zhu, X.Q., Parkinson, J., Kissinger, J.C., Roos, D.S., Sibley, L.D. 2016. Comparative genomic sequence variation of Toxoplasma gondii reveals local admixture drives concerted expansion and diversification of secreted pathogenesis determinants. Nature Genetics. 7:10147.

Interpretive Summary: Toxoplasma gondii is among the most abundant parasites world-wide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its distribution from closely related parasites that typically have narrow, specialized host ranges. We compared the genomes of 62 T. gondii isolates representative of global diversity to several closely related apicomplexan parasites. Our findings reveal that the amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure of T. gondii is characterized by block inheritance of these tandemly clustered determinants, suggesting that they drive evolution of transmission, host range, and pathogencity. This data will be of interest to microbiologists, parasitologists, and biologists interested in the genetics and genomics of infection and disease.

Technical Abstract: Toxoplasma gondii is among the most abundant parasites world-wide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its distribution from closely related parasites that typically have narrow, specialized host ranges. We undertook a comparative genomics approach to understand the diversity of the tissue-cyst forming coccidia focusing on T. gondii and its close relatives. First, we generated additional genomic DNA sequence coverage (~25X coverage) and RNASeq data (>1,000 X mean coverage of coding seqeunce) to improve the assembly and annotation for the reference ME49 strain of T. gondii. We also generated a whole genome sequence for H. hammondi (~65X coverage) and compared these two closely related parasites to the recently completed genomes for S. neurona 21 and N. caninum 22, which cause economically important diseases in horses and cattle, respectively. Finally, to provide insight into genetic variation of T. gondii, we derived whole genome sequences for 62 isolates chosen to span present global diversity. Among this set, 16 reference strains representing the major haplogroups were sequenced by both 454 (3 and 8 kb pair-end libraries) and Illumina (300 bp pair-end libraries) technologies and the resulting reads were assembled and annotated separately (~ 47X average sequence coverage). The remaining strains were sequenced using Illumina only (average ~ 42X average sequence coverage) and were mapped to the reference strain ME49. We used this data to focus on three interpretive themes: 1) Comparison of T. gondii to its most closely related tissue-cyst forming coccidians; 2) Analysis of the core genome of T. gondii and how it has diversified; and 3) Examination of how the global population structure of T. gondii has been shaped by local admixture.