Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression.
Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these 'repressed transcripts' have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies.
School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth PL4 8AA, UK edwin.lasonder@plymouth.ac.uk.
Edwin
0000-0003-2582-3444
E
Lasonder
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Sanna R
SR
Rijpma
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands Malaria Epigenomics Group, Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, The Netherlands.
Ben C L
BC
van Schaijk
Malaria Epigenomics Group, Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, The Netherlands.
Wieteke A M
WA
Hoeijmakers
Malaria Epigenomics Group, Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, The Netherlands.
Philip R
PR
Kensche
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Mark S
MS
Gresnigt
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Annet
A
Italiaander
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Martijn W
MW
Vos
Flow Cytometry Facility, Department of Laboratory Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Rob
R
Woestenenk
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Teun
T
Bousema
Parasitology, Department of Infectious Diseases, University of Heidelberg Medical School, D-69120 Heidelberg, Germany.
Gunnar R
GR
Mair
Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
Shahid M
SM
Khan
Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
Chris J
CJ
Janse
Malaria Epigenomics Group, Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, The Netherlands r.bartfai@science.ru.nl.
Richárd
R
Bártfai
Parasitology, Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands Robert.Sauerwein@radboudumc.nl.
Robert W
RW
Sauerwein
D002843:Chromatin / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D005260:Female; D005718:Gametogenesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014176:Protein Biosynthesis; D020543:Proteome / Q000235:genetics*; D012727:Sex Characteristics; D059467:Transcriptome / Q000235:genetics*
D002843:Chromatin; D020543:Proteome