Project description:To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. However, this species remains enigmatic because it is very challenging to culture, its low parasitaemia in human infections, and frequent co-infection with other malarias . We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis results in 3,699 expressed genes, of which 263 are developmentally regulated and 1,338 are P. malariae-specific, including genes with unknown functions and without orthologs in other Plasmodium. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. We found expressed several members of multigene families, like PIR, PHIST, fam-l, and described new families potentially showing transcriptional heterogeneity. Our findings point to the uniqueness of the P. malariae transcriptome, probably related to different transmission traits in the vector, and the lower pathogenicity and virulence in the human.
Project description:Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri). These species are prevalent across most regions in which malaria is endemic and are often undetectable by light microscopy, rendering their study in human populations difficult. The exact evolutionary relationship of these species to the other human-infective species has been contested. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole.
