Dataset Information

Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

ABSTRACT:

Background

The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions.

Methods

We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima's D) and integrated haplotype score (iHS) to identify genes under selection.

Results

Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima's D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively.

Conclusion

We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known genomic signatures of selection from drug pressure and host immunity. This is evidence that P. falciparum populations explore common adaptive strategies that can be targeted for the development of new interventions.

SUBMITTER: Oyebola KM

PROVIDER: S-EPMC5492182 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

Oyebola Kolapo M KM Idowu Emmanuel T ET Olukosi Yetunde A YA Awolola Taiwo S TS Amambua-Ngwa Alfred A

Parasites & vectors 20170629 1

<h4>Background</h4>The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions.<h4>Methods</h4>We performed a pooled ...[more]

PMID: 28662682

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Project description:The emergence of Plasmodium falciparum drug resistance threatens the efficacy of antimalarial therapies globally. Population genomic studies have been instrumental in mapping malaria genes associated with drug resistance. However, to understand the impact of regional malaria control strategies on the malaria genome, it is necessary to examine parasite subpopulations at the country level. Here, we use selective whole-genome amplification (SWGA) to analyze 120 samples from patients with severe malaria in Mozambique, a country with high malaria burden and risk of emerging drug resistance. We demonstrate that SWGA allows for the generation of near-complete whole-genome sequences from clinical P. falciparum isolates. Our analysis shows that Mozambique parasite genomes show strong diversification of vaccine targets including the circumsporozoite protein (csp), the target of the RTS,S vaccine. Parasites in this population appear fully sensitive to chloroquine, bearing no likely resistance conferring mutations in the chloroquine resistance transporter, pfcrt (PF3D7_0709000) and highly resistant to sulfadoxine-pyrimethamine, exhibiting resistant haplotypes at near fixation. Despite a long history of artemisinin use in Mozambique, we find no evidence of selection near pfkelch13 (PF3D7_1343700) nor evidence of artemisinin resistance conferring mutations in pfkelch13. Using identity by descent analysis, we show positive selection at genomic regions on chromosomes 6, 8, 12, 13, and 14. Gene candidates within these regions include the amino acid transporter 1 (pfaat1, PF3D7_0629500) on chromosome 6 which bears an S258L substitution in >80% of parasites, and a region on chromosome 14 previously amplified under artemisinin pressure.IMPORTANCEMalaria is a devastating disease caused by Plasmodium parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.

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Dataset Information

Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

Background

Methods

Results

Conclusion

Publications

Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

Similar Datasets

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