Transcriptional silencing and activation of paternal DNA during P lasmodium berghei zygotic development and transformation to oocyst

Abstract

SummaryThe malaria parasite develops sexually in the mosquito midgut upon entry with the ingested blood meal before it can invade the midgut epithelium and embark on sporogony. Recent data have identified a number of distinct transcriptional programmes operating during this critical phase of the parasite life cycle. We aimed at characterizing the parental contribution to these transcriptional programmes and establish the genetic framework that would guide further studies of Plasmodium zygotic development and ookinete-to-oocyst transition. To achieve this we used in vitro and in vivo cross-fertilization experiments of various parasite lines expressing fluorescent reporters under the control of constitutive and stage-specific promoters. The results revealed that the zygote/ookinete stage exhibits a maternal phenotype with respect to constitutively expressed reporters, which is derived from either maternal mRNA inheritance or transcription of the maternal allele. The respective paternal alleles are silenced in the zygote/ookinete but reactivated after midgut invasion and transformation to oocyst. Transcripts specifically produced in the zygote/ookinete are synthesized de novo by both parental alleles. These findings highlight a putative role of epigenetic regulation of Plasmodium zygotic development and add substantially to the emerging picture of the molecular mechanisms regulating this important stage of malaria transmission.

Plasmodium berghei P47 is essential for ookinete protection from the Anopheles gambiae complement-like response

“…We investigated the mechanism of P47-mediated protection of ookinetes using an assay whereby the GFP-expressing Δpbp47 parasite line was used together with the mCherry-expressing wt_red 230p line 32 in co-infections of control dsLacZ- injected and LRIM1 knockdown mosquitoes. Our testable hypothesis based on the aforementioned model was that the presence of P47 on mCherry-expressing wt ookinetes would enable some of the GFP-expressing Δpbp47 ookinetes to successfully traverse the midgut epithelium and develop to oocysts by suppressing the signaling response that leads to ookinete nitration.…”

An epigenetic map of malaria parasite development from host to vector

“…While there is no evidence so far that the female gametocyte is transcriptionally poised, there is evidence for the second part of the hypothesis. Firstly, when expression of a fluorescent reporter protein is controlled by an ookinete-specific gene promoter the protein is detected from both the maternal and paternal genomes in the first 24 hours after fertilization 66 . Secondly, if expression of a fluorescent reporter protein is controlled by an housekeeping gene promoter the protein is detected only from the maternal genome 66 .…”

The development of malaria parasites in the mosquito midgut

“…A de novo synthesis study in zygotes identified 91 proteins synthesized only after fertilization, most of which are involved in motility and invasion (Sebastian et al ., 2012). A recent cross‐fertilization study further showed that the zygote/ookinete stage exhibits a maternal phenotype either from maternal mRNA inheritance or transcription of the maternal alleles, while the respective paternal alleles are silenced in these stages (Ukegbu et al ., 2015). Gene expression is further regulated by the apicomplexan transcription factor AP‐O, which associates with more than 500 genes important for ookinete development, motility, midgut penetration and protection against mosquito immunity (Yuda et al ., 2009; Kaneko et al ., 2015).…”