Genetic determinants of gametocyte sex ratio in the human malaria parasite Plasmodium falciparum

Meaden, Cora S.J. (2013) Genetic determinants of gametocyte sex ratio in the human malaria parasite Plasmodium falciparum. PhD thesis, University of Glasgow.

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The aim of this study was to investigate the genetic basis of variation in gametocyte sex ratio in the human malaria parasite, Plasmodium falciparum. The gametocyte sex ratio was measured in progeny clones from the 3D7 x HB3 experimental genetic cross and found to be remarkably stable across replicates of different parasite clones. Significant differences in the sex ratio were observed between the parents of the cross. Progeny clones fell into two classes of sex ratio, one similar to that seen in parent 3D7 and the other like parent HB3, suggesting a single gene of major effect controlling sex ratio. Using a genetic map of the progeny and parental clones, QTL analysis revealed two highly significant loci, the first on chromosome 10 (LOD score = 8.8), and the second on chromosome 14 (LOD = 4.0), linked to gametocyte sex ratio. The locus on chromosome 10, spanning approximately 35kb, contained ten genes. This locus, named PfROS1 (Plasmodium falciparum Ratio of Sex 1), explained 95% of the variation in sex ratio. The second locus on chromosome 14, PfROS2 (Plasmodium falciparum Ratio of Sex 2), explained a small proportion of gametocyte sex ratio variation when combined with PfROS1, the two loci explained 99% of the variation in gametocyte sex ratio observed. As PfROS1 explains such a high percentage of the variation observed in the gametocyte sex ratio it represents a single controlling locus to define the sex ratio of gametocytes produced. This is the first report of a genomic locus influencing gametocyte sex ratio in any Plasmodium species.
In addition, changes in the sex ratio of clones 3D7 and HB3, over the course of 16 days of gametocyte culture were investigated. The number of gametocytes, and especially male gametocytes, was observed to fall markedly in the last few days of culture, when the majority of gametocytes were stage V (mature). Fluctuations in temperature during the culture process were found to influence sex ratio, suggesting the loss of males was due to exflagellation of mature gametocytes. Parasite clone and day of culture were also significant explanatory variables in influencing sex ratio.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Plasmodium falciparum, gametocytes, sex ratio, QTL analysis
Subjects: Q Science > Q Science (General)
Q Science > QL Zoology
Q Science > QR Microbiology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Parasitology
Supervisor's Name: Ranford-Cartwright, Dr. Lisa C.
Date of Award: 2013
Depositing User: Dr. Cora S. J. Meaden
Unique ID: glathesis:2013-4700
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 18 Nov 2013 08:11
Last Modified: 28 Nov 2016 09:23

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