Analysis of transcription of the Plasmodium interspersed repeat (pir) multigene family across the life cycle of Plasmodium species
File(s)
Author(s)
Little, Tim
Type
Thesis
Abstract
The Plasmodium interspersed repeats (pirs) are described as the largest multigene
family found in the genome non-Laveranian species of the malaria parasite,
Plasmodium; however, their function remains unknown. In this thesis, I analyse pir
transcription across the lifecycle of three Plasmodium species, using published and
unpublished data, to identify potential targets for investigating pir function. RNAseq data
from the rodent parasite Plasmodium berghei demonstrated that pir transcription peaks
in the liver merosomes/merozoites, the asexual blood stages, and the male
gametocytes. Detailed analysis of synchronous in vivo asexual blood stages of another
rodent parasite, Plasmodium chabaudi chabaudi, showed that pir transcription peaks in
the late trophozoites. Schizont stages of both rodent species demonstrate an enrichment
for L-form pirs, linking this sub-family to schizogony. With de novo transcriptomics
methods applied to the pirs of the human parasite Plasmodium vivax, I observed that
transcription of pirs in the mosquito stages was minimal, in agreement with the data from
P. berghei. The P. vivax asexual blood cycle pattern of pir transcription also showed
high expression, but timings contrasted to that of P. c. chabaudi as transcription peaked
in late schizonts/early rings. Overall, the results suggest that pirs are important during
the lifecycle stages in the blood, and not in the insect vector. In all three Plasmodium
species, I found the conserved ancestral pir to be highly transcribed, indicative of an
essential function. In conclusion, by collating data from a range of sources I have
identified consistent patterns of pir transcription between Plasmodium species at
different stages of their lifecycle. Based on these results, I have postulated on the
possible role of pirs in the biology of the parasite. This study will enable more targeted
future studies into elucidating the function of this elusive multigene family.
family found in the genome non-Laveranian species of the malaria parasite,
Plasmodium; however, their function remains unknown. In this thesis, I analyse pir
transcription across the lifecycle of three Plasmodium species, using published and
unpublished data, to identify potential targets for investigating pir function. RNAseq data
from the rodent parasite Plasmodium berghei demonstrated that pir transcription peaks
in the liver merosomes/merozoites, the asexual blood stages, and the male
gametocytes. Detailed analysis of synchronous in vivo asexual blood stages of another
rodent parasite, Plasmodium chabaudi chabaudi, showed that pir transcription peaks in
the late trophozoites. Schizont stages of both rodent species demonstrate an enrichment
for L-form pirs, linking this sub-family to schizogony. With de novo transcriptomics
methods applied to the pirs of the human parasite Plasmodium vivax, I observed that
transcription of pirs in the mosquito stages was minimal, in agreement with the data from
P. berghei. The P. vivax asexual blood cycle pattern of pir transcription also showed
high expression, but timings contrasted to that of P. c. chabaudi as transcription peaked
in late schizonts/early rings. Overall, the results suggest that pirs are important during
the lifecycle stages in the blood, and not in the insect vector. In all three Plasmodium
species, I found the conserved ancestral pir to be highly transcribed, indicative of an
essential function. In conclusion, by collating data from a range of sources I have
identified consistent patterns of pir transcription between Plasmodium species at
different stages of their lifecycle. Based on these results, I have postulated on the
possible role of pirs in the biology of the parasite. This study will enable more targeted
future studies into elucidating the function of this elusive multigene family.
Version
Open Access
Date Issued
2022-10
Date Awarded
2023-08
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Langhorne, Jean
Christophides, George
Sponsor
Wellcome Trust (London, England)
Medical Research Council (Great Britain)
Francis Crick Institute
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)