Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in

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Malaria Journal Open Access

RESEARCH

Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana Elikplim A. Amegashie1, Lucas Amenga‑Etego2†, Courage Adobor3, Peter Ogoti1, Kevin Mbogo1, Alfred Amambua‑Ngwa4† and Anita Ghansah3*† 

Abstract  Background:  Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recom‑ bination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods:  Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6–59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data fil‑ tering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geo‑ graphically distinct locations in Ghana. Results:  Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immunodominant TH2R and TH3R vaccine epitopes.

*Correspondence: [email protected] † Lucas Amenga-Etego, Alfred Amambua-Ngwa and Anita Ghansah equally contributed to this work 3 Parasitology Department, Noguchi Memorial Institute of Medical Research, University of Ghana, , Legon, Ghana Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the