Integrated transcriptomic and proteomic analyses of<i>P. falciparum</i>gametocytes: molecular insight into sex-specific processes and translational repression

Lasonder, Edwin; Rijpma, Sanna R.; Schaijk, Ben C. L. van; Hoeijmakers, Wieteke A. M.; Kensche, Philip; Gresnigt, Mark S.; Italiaander, Annet; Vos, Martijn; Woestenenk, Rob; Bousema, Teun; Mair, Gunnar R.; Khan, Shahid M.; Janse, Chris J.; Bártfai, Richárd; Sauerwein, Robert W.

doi:10.1093/nar/gkw536

Cited by 230 publications

(405 citation statements)

References 73 publications

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“…In contrast, a number of MG-enriched proteins function in motility and DNA replication. Such sex-biased proteomes were further corroborated by the recent analysis of sorted P. falciparum MG and FG proteomes (52). Furthermore, we confirmed several of these new predictions of sex partitioning by tagging the endogenous genes with GFP.…”

Section: Discussionsupporting

confidence: 83%

“…These include PfABCG2, two acyl-CoA synthetases, proteins associated with de novo fatty acid synthesis, and enzymes associated with signaling lipid metabolism, which is in agreement with the finding that in P. falciparum there is a high demand for lipids at the gametocyte stage (43,44) and a need of de novo fatty acid synthesis for subsequent development in the free-living environment in a mosquito (42). Comparison with the recent P. falciparum sex-specific/biased proteomes largely confirmed these species-specific differences (supplemental Table S8D) (52).…”

Section: Sex-specific Proteomes Of Human Malaria Parasitesupporting

confidence: 86%

“…Similarly, such type of proteins were also identified in almost all earlier gametocyte proteome work (14,15,18), including the recent P. falciparum sex-specific proteome identified by Lasonder et al (52). Whereas these proteins might be resulted from contaminating asexual stages, it should be rare or impossible in the present and recent studies (52) because both studies used sorted MG and FG that were cultured for an extended period and were supposedly devoid of asexual stages.…”

Section: Discussionsupporting

confidence: 63%

“…S4D, supplemental Table S9A and S9B). Sex-specific/biased Proteins in Plasmodium -Lasonder et al-recently separated mature MG and FG based on marker expression under the male-specific protein dynein heavy chain (PF3D7_1023100) and the female-specific protein Pfs47 and identified 1960 proteins (at least two unique peptides per protein) (52). This combined FG and MG proteome data set showed a strong correlation (r ϭ 0.77) with our combined proteome.…”

Section: Sex-specific Proteomes Of Human Malaria Parasitementioning

confidence: 54%

“…An attempt to identify sex-partitioned proteomes of the P. falciparum gametocytes relied heavily on species-species conservation and bioinformatic predictions (51), and thus might have missed important information underlying the true biological differences between these species. Most recently, a comprehensive proteome analysis of separated P. falciparum MG and FG coupled with transcriptome analysis was reported (52). This study identified divergent MG and FG proteomes similar to the sex-specific proteomes in the gametocytes of P. berghei.…”

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confidence: 73%

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Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes

Miao

Chen

Wang

et al. 2017

Molecular & Cellular Proteomics

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The gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. We generated a transgenic line in the human malaria parasite Plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. In-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female gametocytes, respectively. GFP-tagging of nine selected proteins confirmed their sex-partitions to be agreeable with the results from the proteomic analysis. The sexspecific proteomes showed significant differences that are consistent with the divergent functions of the two sexes. Although the male-specific proteome (119 proteins) is enriched in proteins associated with the flagella and genome replication, the female-specific proteome (262 proteins) is more abundant in proteins involved in metabolism, translation and organellar functions. Compared with the Plasmodium berghei sex-specific proteomes, this study revealed both extensive conservation and considerable divergence between these two species, which reflect the disparities between the two species in proteins involved in cytoskeleton, lipid metabolism and protein degradation. Comparison with three sex-specific proteomes allowed us to obtain high-confidence lists of 73 and 89 core male-and female-specific/biased proteins conserved in Plasmodium. The identification of sex-specific/biased proteomes in Plasmodium lays a solid foundation for understanding the molecular mechanisms underlying the unique sex-specific biology in this earlybranching eukaryote. Molecular & Cellular Proteomics

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Section: Discussionsupporting

confidence: 83%

Section: Sex-specific Proteomes Of Human Malaria Parasitesupporting

confidence: 86%

Section: Discussionsupporting

confidence: 63%

Section: Sex-specific Proteomes Of Human Malaria Parasitementioning

confidence: 54%

mentioning

confidence: 73%

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Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes

Miao

Chen

Wang

et al. 2017

Molecular & Cellular Proteomics

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Uracil moieties in Plasmodium falciparum genomic DNA

et al. 2018

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Plasmodium falciparum parasites undergo multiple genome duplication events during their development. Within the intraerythrocytic stages, parasites encounter an oxidative environment and DNA synthesis necessarily proceeds under these circumstances. In addition to these conditions, the extreme AT bias of the P. falciparum genome poses further constraints for DNA synthesis. Taken together, these circumstances may allow appearance of damaged bases in the Plasmodium DNA . Here, we focus on uracil that may arise in DNA either via oxidative deamination or thymine‐replacing incorporation. We determine the level of uracil at the ring, trophozoite, and schizont intraerythrocytic stages and evaluate the base‐excision repair potential of P. falciparum to deal with uracil‐ DNA repair. We find approximately 7–10 uracil per million bases in the different parasite stages. This level is considerably higher than found in other wild‐type organisms from bacteria to mammalian species. Based on a systematic assessment of P. falciparum genome and transcriptome databases, we conclude that uracil‐ DNA repair relies on one single uracil‐ DNA glycosylase and proceeds through the long‐patch base‐excision repair route. Although potentially efficient, the repair route still leaves considerable level of uracils in parasite DNA , which may contribute to mutation rates in P. falciparum .

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EuPathDB: The Eukaryotic Pathogen Genomics Database Resource

Warrenfeltz

Basenko

Crouch

et al. 2018

Methods in Molecular Biology

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The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host-pathogen interactions.

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Integrated transcriptomic and proteomic analyses ofP. falciparumgametocytes: molecular insight into sex-specific processes and translational repression

Cited by 230 publications

References 73 publications

Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes

Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes

Uracil moieties in Plasmodium falciparum genomic DNA

EuPathDB: The Eukaryotic Pathogen Genomics Database Resource

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