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Metabolic and molecular evidence of adenosine kinase activity in Plasmodium falciparum [Meeting Abstract]
Cassera, MB; Merino, EF; Hazleton, KZ; Carlton, JM; Schramm, VL
ISI:000253127600199
ISSN: 0020-7519
CID: 76168
Carotenoid biosynthesis in the intraerythrocytic stages of Plasmodium falciparum [Meeting Abstract]
D'Alexandri, FL; Tonhosolo, R; de Rosso, VV; Dutra, MG; Merino, EF; Wunderlich, G; Carlton, JM; Mercadante, AZ; Kimura, EA; Katzin, AM
ISI:000253127600230
ISSN: 0020-7519
CID: 76169
Hunting down the genetic determinants of Plasmodium vivax chloroquine resistance [Meeting Abstract]
Kang'a, S; Merino, EF; Susanti, AI; Leksana, B; Maguire, JD; Carlton, JM
ISI:000253127600215
ISSN: 0020-7519
CID: 98144
Within-host and population-level genetic diversity of Plasmodium vivax in Peru [Meeting Abstract]
Sutton, PL; Kang'a, S; Hernandez, JN; Merino, EF; Vidal, CE; Carlton, J; Branch, OH
ISI:000250758201309
ISSN: 0002-9637
CID: 98152
Contrasting genetic structure in Plasmodium vivax populations from Asia and South America
Imwong, Mallika; Nair, Shalini; Pukrittayakamee, Sasithon; Sudimack, Daniel; Williams, Jeff T; Mayxay, Mayfong; Newton, Paul N; Kim, Jung Ryong; Nandy, Amitab; Osorio, Lyda; Carlton, Jane M; White, Nicholas J; Day, Nicholas P J; Anderson, Tim J C
Populations of Plasmodium falciparum show striking differences in linkage disequilibrium, population differentiation and diversity, but only fragmentary data exists on the genetic structure of Plasmodium vivax. We genotyped nine tandem repeat loci bearing 2-8bp motifs from 345 P. vivax infections collected from three Asian countries and from five locations in Colombia. We observed 9-37 alleles per locus and high diversity (H(e)=0.72-0.79, mean=0.75) in all countries. Numbers of multiple clone infections varied considerably: these were rare in Colombia and India, but > 60% of isolates carried multiple alleles in at least one locus in Thailand and Laos. However, only one or two of the nine loci show >1 allele in many samples, suggesting that mutation within infections may result in overestimation of true multiple carriage rates. Identical nine-locus genotypes were frequently found in Colombian populations, contributing to strong linkage disequilibrium. These identical genotypes were strongly clustered in time, consistent with epidemic transmission of clones and subsequent breakdown of allelic associations, suggesting high rates of inbreeding and low effective recombination rates in this country. In contrast, identical genotypes were rare and loci were randomly associated in all three Asian populations, consistent with higher rates of outcrossing and recombination. We observed low but significant differentiation between different Asian countries (standardized F(ST)=0.13-0.45). In comparison, we see greater differentiation between collection locations within Colombia (standardized F(ST)=0.4-0.7), and strong differentiation between continents (standardized F(ST)=0.48-0.79). The observed heterogeneity in multiple clone carriage rates, linkage disequilibrium and population differentiation are similar in some, but not all, respects to those observed in P. falciparum, and have important implications for the design of association mapping studies, and interpretation of P. vivax epidemiology
PMID: 17442318
ISSN: 0020-7519
CID: 72021
Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites
Imwong, Mallika; Snounou, Georges; Pukrittayakamee, Sasithon; Tanomsing, Naowarat; Kim, Jung Ryong; Nandy, Amitab; Guthmann, Jean-Paul; Nosten, Francois; Carlton, Jane; Looareesuwan, Sornchai; Nair, Shalini; Sudimack, Daniel; Day, Nicholas P J; Anderson, Timothy J C; White, Nicholas J
BACKGROUND: Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection. METHODS: Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n=36), where reinfection could be excluded, and during field studies in Myanmar (n=75) and India (n=38). RESULTS: Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection. CONCLUSIONS: The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria
PMID: 17330781
ISSN: 0022-1899
CID: 72022
Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis
Carlton, Jane M; Hirt, Robert P; Silva, Joana C; Delcher, Arthur L; Schatz, Michael; Zhao, Qi; Wortman, Jennifer R; Bidwell, Shelby L; Alsmark, U Cecilia M; Besteiro, Sebastien; Sicheritz-Ponten, Thomas; Noel, Christophe J; Dacks, Joel B; Foster, Peter G; Simillion, Cedric; Van de Peer, Yves; Miranda-Saavedra, Diego; Barton, Geoffrey J; Westrop, Gareth D; Muller, Sylke; Dessi, Daniele; Fiori, Pier Luigi; Ren, Qinghu; Paulsen, Ian; Zhang, Hanbang; Bastida-Corcuera, Felix D; Simoes-Barbosa, Augusto; Brown, Mark T; Hayes, Richard D; Mukherjee, Mandira; Okumura, Cheryl Y; Schneider, Rachel; Smith, Alias J; Vanacova, Stepanka; Villalvazo, Maria; Haas, Brian J; Pertea, Mihaela; Feldblyum, Tamara V; Utterback, Terry R; Shu, Chung-Li; Osoegawa, Kazutoyo; de Jong, Pieter J; Hrdy, Ivan; Horvathova, Lenka; Zubacova, Zuzana; Dolezal, Pavel; Malik, Shehre-Banoo; Logsdon, John M Jr; Henze, Katrin; Gupta, Arti; Wang, Ching C; Dunne, Rebecca L; Upcroft, Jacqueline A; Upcroft, Peter; White, Owen; Salzberg, Steven L; Tang, Petrus; Chiu, Cheng-Hsun; Lee, Ying-Shiung; Embley, T Martin; Coombs, Graham H; Mottram, Jeremy C; Tachezy, Jan; Fraser-Liggett, Claire M; Johnson, Patricia J
We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria
PMCID:2080659
PMID: 17218520
ISSN: 1095-9203
CID: 72023
Comparative genomics and the development of antimalarial and antiparasitic therapeutics
Chapter by: Merino, Emilio F.; Sullivan, Steven A.; Carlton, Jane M.
in: Comparative Genomics: Basic and Applied Research by
[S.l.] : CRC Press, 2007
pp. 193-218
ISBN: 9780849392160
CID: 4669882
Toward a malaria haplotype map [Comment]
Carlton, Jane M
PMID: 17192778
ISSN: 1061-4036
CID: 72024
Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote
Eisen, Jonathan A; Coyne, Robert S; Wu, Martin; Wu, Dongying; Thiagarajan, Mathangi; Wortman, Jennifer R; Badger, Jonathan H; Ren, Qinghu; Amedeo, Paolo; Jones, Kristie M; Tallon, Luke J; Delcher, Arthur L; Salzberg, Steven L; Silva, Joana C; Haas, Brian J; Majoros, William H; Farzad, Maryam; Carlton, Jane M; Smith, Roger K Jr; Garg, Jyoti; Pearlman, Ronald E; Karrer, Kathleen M; Sun, Lei; Manning, Gerard; Elde, Nels C; Turkewitz, Aaron P; Asai, David J; Wilkes, David E; Wang, Yufeng; Cai, Hong; Collins, Kathleen; Stewart, B Andrew; Lee, Suzanne R; Wilamowska, Katarzyna; Weinberg, Zasha; Ruzzo, Walter L; Wloga, Dorota; Gaertig, Jacek; Frankel, Joseph; Tsao, Che-Chia; Gorovsky, Martin A; Keeling, Patrick J; Waller, Ross F; Patron, Nicola J; Cherry, J Michael; Stover, Nicholas A; Krieger, Cynthia J; del Toro, Christina; Ryder, Hilary F; Williamson, Sondra C; Barbeau, Rebecca A; Hamilton, Eileen P; Orias, Eduardo
The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance
PMCID:1557398
PMID: 16933976
ISSN: 1545-7885
CID: 68202