Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites
Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of para...
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Public Library of Science
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486833/ |
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pubmed-34868332012-11-06 Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites Amambua-Ngwa, Alfred Tetteh, Kevin K. A. Manske, Magnus Gomez-Escobar, Natalia Stewart, Lindsay B. Deerhake, M. Elizabeth Cheeseman, Ian H. Newbold, Christopher I. Holder, Anthony A. Knuepfer, Ellen Janha, Omar Jallow, Muminatou Campino, Susana MacInnis, Bronwyn Kwiatkowski, Dominic P. Conway, David J. Research Article Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now prioritized for functional study. Public Library of Science 2012-11-01 /pmc/articles/PMC3486833/ /pubmed/23133397 http://dx.doi.org/10.1371/journal.pgen.1002992 Text en © 2012 Amambua-Ngwa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Amambua-Ngwa, Alfred Tetteh, Kevin K. A. Manske, Magnus Gomez-Escobar, Natalia Stewart, Lindsay B. Deerhake, M. Elizabeth Cheeseman, Ian H. Newbold, Christopher I. Holder, Anthony A. Knuepfer, Ellen Janha, Omar Jallow, Muminatou Campino, Susana MacInnis, Bronwyn Kwiatkowski, Dominic P. Conway, David J. |
| spellingShingle |
Amambua-Ngwa, Alfred Tetteh, Kevin K. A. Manske, Magnus Gomez-Escobar, Natalia Stewart, Lindsay B. Deerhake, M. Elizabeth Cheeseman, Ian H. Newbold, Christopher I. Holder, Anthony A. Knuepfer, Ellen Janha, Omar Jallow, Muminatou Campino, Susana MacInnis, Bronwyn Kwiatkowski, Dominic P. Conway, David J. Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| author_facet |
Amambua-Ngwa, Alfred Tetteh, Kevin K. A. Manske, Magnus Gomez-Escobar, Natalia Stewart, Lindsay B. Deerhake, M. Elizabeth Cheeseman, Ian H. Newbold, Christopher I. Holder, Anthony A. Knuepfer, Ellen Janha, Omar Jallow, Muminatou Campino, Susana MacInnis, Bronwyn Kwiatkowski, Dominic P. Conway, David J. |
| author_sort |
Amambua-Ngwa, Alfred |
| title |
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| title_short |
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| title_full |
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| title_fullStr |
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| title_full_unstemmed |
Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites |
| title_sort |
population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites |
| description |
Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now prioritized for functional study. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486833/ |
| _version_ |
1611920637743333376 |