Stable allele frequency distribution of the polymorphic region of SURFIN4.2 in Plasmodium falciparum isolates from Thailand

Kaewthamasorn, Morakot; Yahata, Kazuhide; Alexandre, Jean Semé Fils; Xangsayarath, Phonepadith; Nakazawa, Shozo; Torii, Motomi; Sattabongkot, Jetsumon; Udomsangpetch, Rachanee; Kaneko, O.

doi:10.1016/j.parint.2011.12.003

Cited by 10 publications

(22 citation statements)

References 21 publications

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“…A total of 405 polymorphic nucleotide sites and 9 insertion/deletions (indels; AAT at nt 1348–1350, TAC between nt 1746–1747 and GGA between nt 2274–2274) were observed among 63 sequences with an average pairwise nucleotide diversity of 0.069. These values were higher than those for surf 4.2 obtained from the 74 sequences originating from a similar set of Thai samples (among 67 isolates used for surf 4.2 , 9 isolates were excluded and 5 isolates were newly added for this surf 4.1 analysis), which showed 255 polymorphic sites out of 2166 bp with an average pairwise nucleotide diversity of 0.043 [10]. To evaluate the area(s) accumulating polymorphisms as we did for SURFIN 4.2 , we again divided the extracellular region of SURFIN 4.1 into three regions based on amino acid sequence conservation among SURFIN members: N-terminal segment (Nter; amino acid positions (aa) 1–50, nt 1–150), CRD (aa 51–195, nt 151–585), and a variable region (aa 196–770, nt 586–2310).…”

Section: Resultsmentioning

confidence: 85%

“…In addition, one sequence was obtained from a sample originating from Myanmar, which was different from all 37 haplotypes found in Thai parasite lines. Because 11 haplotypes contained more than one sequence, we checked other gene loci ( surf 4.2 , clag2 , clag8 , clag9 , and 18 putatively neutral loci), which were determined for most of the isolates evaluated in this study [10, 23, 24] to see if any of them showed the same genetic background. We found that all sequences possessed distinct allele status for at least one SNP, except MS841, for which other gene loci were not determined, confirming that they had different genetic backgrounds.…”

Section: Resultsmentioning

confidence: 99%

“…Ochola et al (2010) performed a genome wide survey to identify novel polymorphic genes and found that another SURFIN member, SURFIN 4.2 , was highly polymorphic and that the signature of positive selection was acting on this gene locus using P. falciparum samples from Kenya [9]. Positive diversifying selection on this gene was further validated in the Thai P. falciparum population [10]. However, the analysis of surf 4.1 diversity using Kenyan isolates found surf 4.1 , encoding SURFIN 4.1 , under purifying selection rather than positive selection.…”

Section: Introductionmentioning

confidence: 99%

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Positive Diversifying Selection on the Plasmodium falciparum surf4.1 Gene in Thailand

et al. 2012

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Plasmodium falciparum SURFIN4.1 is a type I transmembrane protein thought to locate on the merozoite surface and to be responsible for a reversible adherence to the erythrocyte before invasion. In this study, we evaluated surf4.1 gene segment encoding extracellular region for polymorphism, the signature of positive selection, the degree of linkage disequilibrium, and temporal change in allele frequency distribution in P. falciparum isolates from Thailand in 1988–89, 2003, and 2005. We found that SURFIN4.1 is highly polymorphic, particularly at the C-terminal side of the variable region located just before a predicted transmembrane region. A signature of positive diversifying selection on the variable region was detected by multiple tests and, to a lesser extent, on conserved N-terminally located cysteine-rich domain by Tajima’s D test. Linkage disequilibrium between sites over a long distance (> 1.5 kb) was detected, and multiple SURFIN4.1 haplotype sequences detected in 1988/89 still circulated in 2003. Few of the single amino acid polymorphism allele frequency distributions were significantly different between the 1988/89 and 2003 groups, suggesting that the frequency distribution of SURFIN4.1 extracellular region remained stable over 14 years.

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Positive Diversifying Selection on the Plasmodium falciparum surf4.1 Gene in Thailand

et al. 2012

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“…Previous analyses of microsatellites and single nucleotide polymorphisms (SNP) have identified selective sweeps around several previously-identified drug resistance genes, encouraging genome wide analyses to prospect for other chromosomal loci containing genes under recent positive directional selection [10], [11], [12]. Separately, studies of individual genes encoding surface-exposed protein targets of acquired immunity have shown signatures of balancing selection maintaining different alleles within populations (reviewed in [13]), and these results replicate well in independent studies of different endemic populations [13], [14], [15], [16], [17]. This indicates that new potential candidates for vaccine development based on multi-allelic antigen formulations might be identified with a systematic genome-wide scan for such signatures in an endemic population.…”

Section: Introductionmentioning

confidence: 80%

Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites

et al. 2012

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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.

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“…surf 4.1 gene region encoding SURFIN 4.1 extracellular region possesses more polymorphic sites than the corresponding region of the surf 4.2 gene. Significant positive deviations of Tajima’s D value from zero were detected on surf 4.2 in both Thai and Kenyan parasite populations and positive selection was proposed on this gene [15, 16]. However, this is not the case for surf 4.1 , for which positively deviated Tajima’s D values were detected in Thai P. falciparum population [17], but negatively deviated values in the parasite population from Ngerenye area of Kilifi, eastern Kenya [15].…”

Section: Introductionmentioning

confidence: 99%

Selections, frameshift mutations, and copy number variation detected on the surf 4.1 gene in the western Kenyan Plasmodium falciparum population

Gitaka

Takeda

Kimura

et al. 2017

Malar J

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Background Plasmodium falciparum SURFIN4.1 is a putative ligand expressed on the merozoite and likely on the infected red blood cell, whose gene was suggested to be under directional selection in the eastern Kenyan population, but under balancing selection in the Thai population. To understand this difference, surf 4.1 sequences of western Kenyan P. falciparum isolates were analysed. Frameshift mutations and copy number variation (CNV) were also examined for the parasites from western Kenya and Thailand.ResultsPositively significant departures from neutral expectations were detected on the surf 4.1 region encoding C-terminus of the variable region 2 (Var2) by 3 population-based tests in the western Kenyan population as similar in the Thai population, which was not covered by the previous analysis for eastern Kenyan population. Significant excess of non-synonymous substitutions per nonsynonymous site over synonymous substitutions per synonymous site was also detected in the Var2 region. Negatively significant departures from neutral expectations was detected on the region encoding Var1 C-terminus consistent to the previous observation in the eastern Kenyan population. Parasites possessing a frameshift mutation resulting a product without intracellular Trp-rich (WR) domains were 22/23 in western Kenya and 22/36 in Thailand. More than one copy of surf 4.1 gene was detected in western Kenya (4/24), but no CNV was found in Thailand (0/36).ConclusionsThe authors infer that the high polymorphism of SURFIN4.1 Var2 C-terminus in both Kenyan and Thai populations were shaped-up by diversifying selection and maintained by balancing selection. These phenomena were most likely driven by immunological pressure. Whereas the SURFIN4.1 Var1 C-terminus is suggested to be under directional selection consistent to the previous report for the eastern Kenyan population. Most western Kenyan isolates possess a frameshift mutation that would limit the expression of SURFIN4.1 on the merozoite, but only 60% of Thai isolates possess this frameshift, which would affect the level and type of the selection pressure against this protein as seen in the two extremities of Tajima’s D values for Var1 C-terminus between Kenyan and Thai populations. CNV observed in Kenyan isolates may be a consequence of this frameshift mutation to increase benefits on the merozoite surface.

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Stable allele frequency distribution of the polymorphic region of SURFIN4.2 in Plasmodium falciparum isolates from Thailand

Cited by 10 publications

References 21 publications

Positive Diversifying Selection on the Plasmodium falciparum surf4.1 Gene in Thailand

Positive Diversifying Selection on the Plasmodium falciparum surf4.1 Gene in Thailand

Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites

Selections, frameshift mutations, and copy number variation detected on the surf 4.1 gene in the western Kenyan Plasmodium falciparum population

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