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Genomic analysis reveals independent evolution of Plasmodium falciparum population in Ethiopia
Lemu Golassa
Addis Ababa University, Aklilu Lemma Institute of Pathobiology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1216-8711
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Plasmodium falciparum parasite populations have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from central area of Ethiopia.
Method
: Whole genome analysis of 25 P. falciparum isolates from central Ethiopia were made to determine their genetic diversity, population structures and signatures of selection in known drug resistance loci against isolates from Cambodia, Thailand, DR Congo and Malawi.
Result
A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified with average nucleotide diversity (π = 0.00022) across the genome. About 84% of the Ethiopian P. falciparum isolates had FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within host diversity of Ethiopian infections was significantly different from East African (p < 0.001) but not Southeast Asian infections (P > 0.05). A significant population structure differentiation between Ethiopian parasites and East Africa (Fst < 10%) and Southeast Asia populations (Fst ~ 18%) has been observed, suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection is identified that included ama1, trap, eba175, and lsa3 previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the pfcrt, pfdhfr, pfdhps, pfmdr1, and pfK13 genes. However, mutations analysis showed that at least one SNP marker was fixed in these genes, but not in pfdhps and pfK13.
Conclusion
Plasmodium falciparum population in central region of Ethiopia were structurally diverged from both southeast Asian and other East African populations. A low within host diversity is noted among the Ethiopian parasites. Indeed, the parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.
Keywords
Plasmodium falciparum, Ethiopia, population structure, drug resistance, admixture, positive selection
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CURRENT STATUS: Under Review
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Posted 18 Sep, 2020
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Editorial decision: Major Revision
On 26 Nov, 2020
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Received 23 Nov, 2020
Review #1 received
Received 05 Nov, 2020
Reviewer #2 agreed
On 01 Nov, 2020
Reviewer #1 agreed
On 26 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Editor assigned
On 15 Sep, 2020
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On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
First submitted
On 09 Sep, 2020
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Subject Areas
General Biochemistry
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This preprint is under consideration at Malaria Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Genomic analysis reveals independent evolution of Plasmodium falciparum population in Ethiopia
Lemu Golassa
Addis Ababa University, Aklilu Lemma Institute of Pathobiology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1216-8711
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Sep, 2020
No community comments so far
Editorial decision: Major Revision
On 26 Nov, 2020
Review #2 received
Received 23 Nov, 2020
Review #1 received
Received 05 Nov, 2020
Reviewer #2 agreed
On 01 Nov, 2020
Reviewer #1 agreed
On 26 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Editor assigned
On 15 Sep, 2020
Submission checks complete
On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
First submitted
On 09 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Biochemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Plasmodium falciparum parasite populations have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from central area of Ethiopia.
Method
: Whole genome analysis of 25 P. falciparum isolates from central Ethiopia were made to determine their genetic diversity, population structures and signatures of selection in known drug resistance loci against isolates from Cambodia, Thailand, DR Congo and Malawi.
Result
A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified with average nucleotide diversity (π = 0.00022) across the genome. About 84% of the Ethiopian P. falciparum isolates had FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within host diversity of Ethiopian infections was significantly different from East African (p < 0.001) but not Southeast Asian infections (P > 0.05). A significant population structure differentiation between Ethiopian parasites and East Africa (Fst < 10%) and Southeast Asia populations (Fst ~ 18%) has been observed, suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection is identified that included ama1, trap, eba175, and lsa3 previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the pfcrt, pfdhfr, pfdhps, pfmdr1, and pfK13 genes. However, mutations analysis showed that at least one SNP marker was fixed in these genes, but not in pfdhps and pfK13.
Conclusion
Plasmodium falciparum population in central region of Ethiopia were structurally diverged from both southeast Asian and other East African populations. A low within host diversity is noted among the Ethiopian parasites. Indeed, the parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7