Estimating the micro-indel mutation rate in Plasmodium falciparum using genomes from mutation accumulation experiments

Singh, Aakanksha (2021) Estimating the micro-indel mutation rate in Plasmodium falciparum using genomes from mutation accumulation experiments. Master's Research Project 1, Ecology and Evolution.

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Abstract

Malaria is a life threatening disease caused by parasites of the Plasmodium genus. Infection with P. falciparum single handedly accounts for more than 90% of the world’s malaria mortality. The global fight against malaria has repeatedly been compromised by drug-resistant P. falciparum strains that first emerged in South East Asia. Despite Africa bearing the largest disease load, South East Asia has been the hotspot of the evolution of drug resistance in malaria. P. falciparum has a unique genome that is eighty percent AT rich, providing adequate opportunities for mutations. The underlying mutations aid in the selection of drug-resistant strains in an environment where drugs are prevalent. I hypothesized that Asian strains have a higher rate of micro-indel mutations as compared to the African strains of P. falciparum. To test the hypothesis, I used data from Claessens et al. (2014) who generated six clone trees of P. falciparum strains that belong to four geographically distinct regions. Hamilton et al (2016) used the same data to calculate SNP mutation rate in the six strains. I extended the experiment to calculate the micro-indel mutation rate, which could now be appropriately calculated after the publication of twelve newly assembled PacBio reference genomes for P. falciparum strains, which also include the strains that were used for clone tree generation. I created a GATK-based pipeline to detect, for the first time, micro-indels in non-3D7 strains. My analysis suggests that the micro-indel mutation rate of 3D7, the strain from Africa, has a slightly lower mutation rate than Dd2 and W2, the strains with Asian origin.

Item Type:	Thesis (Master's Research Project 1)
Supervisor name:	Beukeboom, L.W.
Degree programme:	Ecology and Evolution
Thesis type:	Master's Research Project 1
Language:	English
Date Deposited:	19 May 2021 15:28
Last Modified:	19 May 2021 15:31
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/24424

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