title: Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology.
abstract: One of the critical gaps in malaria transmission biology and surveillance is our lack of knowledge about Plasmodium falciparum gametocyte biology, especially sexual dimorphic development and how sex ratios that may influence transmission from the human to the mosquito. Dissecting this process has been hampered by the lack of sex-specific protein markers for the circulating, mature stage V gametocytes. The current evidence suggests a high degree of conservation in gametocyte gene complement across Plasmodium, and therefore presumably for sex-specific genes as well. To better our understanding of gametocyte development and subsequent infectiousness to mosquitoes, we undertook a Systematic Subtractive Bioinformatic analysis (filtering) approach to identify sex-specific P. falciparum NF54 protein markers based on a comparison with the Dd2 strain, which is defective in producing males, and with syntenic male and female proteins from the reanalyzed and updated P. berghei (related rodent malaria parasite) gametocyte proteomes. This produced a short list of 174 male- and 258 female-enriched P. falciparum stage V proteins, some of which appear to be under strong diversifying selection, suggesting ongoing adaptation to mosquito vector species. We generated antibodies against three putative female-specific gametocyte stage V proteins in P. falciparum and confirmed either conserved sex-specificity or the lack of cross-species sex-partitioning. Finally, our study provides not only an additional resource for mass spectrometry-derived evidence for gametocyte proteins but also lays down the foundation for rational screening and development of novel sex-partitioned protein biomarkers and transmission-blocking vaccine candidates.
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA;
authors: Dingyin
authors: D
authors: Tao
authors: §Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, Maryland, USA;
authors: Ceereena
authors: C
authors: Ubaida-Mohien
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA;
authors: Derrick K
authors: DK
authors: Mathias
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA;
authors: Jonas G
authors: JG
authors: King
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA;
authors: Rebecca
authors: R
authors: Pastrana-Mena
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA;
authors: Abhai
authors: A
authors: Tripathi
authors: ¶Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts, USA;
authors: Ilana
authors: I
authors: Goldowitz
authors: §Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, Maryland, USA;
authors: David R
authors: DR
authors: Graham
authors: ‖The Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA.
authors: Eli
authors: E
authors: Moss
authors: ¶Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts, USA;
authors: Matthias
authors: M
authors: Marti
authors: From the ‡W. Harry Feinstone Department of Molecular Microbiology and Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland, USA; rdinglasan@jhu.edu.
authors: Rhoel R
authors: RR
authors: Dinglasan
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008018:Life Cycle Stages; D008297:Male; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000032:analysis*; D012737:Sex Factors
chemical_list: D015800:Protozoan Proteins