Evolution of allelic dimorphism in malarial surface antigens

Roy, Scott William; Ferreira, Marcelo U.; Hartl, Daniel L.

doi:10.1038/sj.hdy.6800887

Cited by 32 publications

(58 citation statements)

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“…Thus, polymorphism of clag2 and 8 appears to be generated between the divergence of P. falciparum and P. reichenowi and TMRCA of the extant P. falciparum populations. Early origins of the polymorphism have been suggested for merozoite surface proteins PfMSP-1 and PfMSP-2, for which the origin of the polymorphism was proposed to predate the P. falciparum-P. reichenowi divergence (thus termed 'ancient origin'), or TMRCA of the extant P. falciparum population, respectively [53,54]. Early origins of the polymorphism older than TMRCA of extant P. falciparum populations would suggest that rhoph1/clag polymorphisms confer an advantage to the parasite and were positively selected for during the recent evolution of P. falciparum.…”

Section: Evolution Of Pfrhoph1/clag Polymorphism Of the Extant P Falmentioning

confidence: 99%

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Iriko

Kaneko

Otsuki

et al. 2008

Molecular and Biochemical Parasitology

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A complex of high molecular mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Understanding the level of polymorphism and the evolutionary processes is important for advancements in both vaccine design and knowledge of the evolution of cell invasion in this parasite. In the present study, we sequenced the entire open reading frames of seven genes encoding the proteins of the PfRhopH complex (rhoph2, rhoph3, and five rhoph1/clag gene paralogs). We found that four rhoph1/clag genes (clag2, 3.1, 3.2, and 8) were highly polymorphic. Amino acid substitutions and indels are predominantly clustered around amino acid positions 1000-1200 of these four rhoph1/clag genes. An excess of nonsynonymous substitutions over synonymous substitutions was detected for clag8 and 9, indicating positive selection. The McDonald-Kreitman test with a Plasmodium reichenowi orthologous sequence also supports positive selection on clag8. Based on the ratio of interspecific genetic distance to intraspecific distance, the time to the most recent common ancestor of the clag2 and 8 polymorphisms was estimated to be 1.89 and 0.87 million years ago, respectively, assuming divergence of P. falciparum and P. reichenowi 6 million years ago. In addition to a copy number polymorphism, gene conversion events were detected for the rhoph1/clag genes on chromosome 3, which likely play a role in increasing the diversity of each locus. Our results indicate that a high diversity of the PfRhopH1/Clag multigene family is maintained by diversifying selection forces over a considerably long period.

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Section: Evolution Of Pfrhoph1/clag Polymorphism Of the Extant P Falmentioning

confidence: 99%

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Iriko

Kaneko

Otsuki

et al. 2008

Molecular and Biochemical Parasitology

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“…The wellcharacterised polymorphic regions in these genes have been extensively used to analyse genetic diversity patterns in P. falciparum (Roy et al 2008). A similar approach has been explored in vivax-oriented studies (Cui et al 2003a).…”

Section: Abstract: Malaria -Plasmodium Vivax -Genetic Markers -Genetmentioning

confidence: 99%

“…vivax evidences an allelic form diversity across the msp1 gene. In contrast, P. falciparum exhibits a clear allelic dimorphism over a long region in the msp1 locus (that is, sequences can be grouped into 1 of 2 major allelic types, MAD20 and K1) (Roy et al 2008). Fre- Fig.…”

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confidence: 99%

Molecular markers and genetic diversity of Plasmodium vivax

Brito

Ferreira

2011

Mem. Inst. Oswaldo Cruz

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Enhanced understanding of the transmission dynamics and population genetics for Key words: malaria -Plasmodium vivax -genetic markers -genetic diversity -multiple-clone infections -microsatellitesMarkers and genetic diversity of P. vivax • Cristiana Ferreira Alves de Brito, Marcelo Urbano Ferreira 13 tual heterozygosity (H E ) values. Virtual H E is the average probability that a pair of alleles randomly obtained from the population is different. Whenever appropriate, in this review we provide H E estimates obtained using different markers for different populations.Molecular markers under selection -Until recently, most genetic markers available for characterising natural P. vivax populations were orthologues of previously identified P. falciparum antigen-coding genes. The wellcharacterised polymorphic regions in these genes have been extensively used to analyse genetic diversity patterns in P. falciparum (Roy et al. 2008). A similar approach has been explored in vivax-oriented studies (Cui et al. 2003a). The following single-copy genes in P. vivax have often been used in these studies: gam1, coding for the gametocyte antigen 1, csp, coding for the circumsporozoite protein (CSP), msp1 and msp3alpha, coding for the merozoite surface proteins (MSP)-1 and 3α, respectively, ama1, coding for the apical membrane antigen 1, and dbp, coding for the Duffy binding protein (DBP) ( Table I).A notable feature of several P. vivax surface antigens (including major vaccine-candidate molecules) is tandem arrays of relatively short amino acid motifs. The CSP in P. vivax (PvCSP), an abundant antigen on the surface of sporozoites that has been extensively used as a vaccine development target, has immunodominant B-cell epitopes that map to central repeats between nonrepetitive sequences (Nardin & Zavala 1998). PvCSP displays two major types of nonapeptide repeats [most commonly GDRA(D/A)GQPA and ANGA(G/D)(N/D)QPG], which define the variants known as VK210 and VK247, respectively (Arnot et al. 1985, Rosenberg et al. 1989 (Fig. 1). Both VK210 and VK247 variants are globally distributed, but geographic biases have been described (Cochrane et al. 1990, Qari et al. 1993a. Similar repetitive sequences are found in Brazil, Southeast Asia and Papua New Guinea (Qari et al. 1991(Qari et al. , 1992. However, markedly divergent sequence variants were found in isolates from China and North Korea (Mann et al. 1994). Although VK210 and VK247-type sequences often occur in sympatric parasite populations, there are no examples of a hybrid repeat array with both repeat types (Lim et al. 2005).A third type of repeat unit [APGANQ(E/G)GAA], identical to that described for Plasmodium simiovale, characterises the so-called P. vivax-like parasites (Qari et al. 1993a). Although P. vivax-like CSP repeats have been found in parasite isolates across the world, its global distribution remains unconfirmed (Gopinath et al. 1994). In Brazil, P. vivax-like parasites have been identified only in mixed-clone infections with VK210-type or VK247-type parasites (Machado...

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“…Little is known about variation in noncoding regions, which could have a significant impact on phenotype by regulating gene expression (Gonzales et al 2008;Mok et al 2014). Knowledge of complex variation, where haplotypes are highly diverged from the reference genome, is constrained to a few wellstudied genes such as msp1 (Roy et al 2008). A critical step in overcoming these obstacles is to have a reliable, empirical indicator of genotyping error, which allows genotyping methods to be calibrated and compared.…”

Section: Ox1 3lb United Kingdommentioning

confidence: 99%

Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum

et al. 2016

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The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable and thus difficult to analyze using short-read sequencing technologies. Here, we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first genome-wide, integrated analysis of SNP, indel and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that indels are exceptionally abundant, being more common than SNPs and thus the dominant mode of polymorphism within the core genome. We use the high density of SNP and indel markers to analyze patterns of meiotic recombination, confirming a high rate of crossover events and providing the first estimates for the rate of non-crossover events and the length of conversion tracts. We observe several instances of meiotic recombination within copy number variants associated with drug resistance, demonstrating a mechanism whereby fitness costs associated with resistance mutations could be compensated and greater phenotypic plasticity could be acquired.

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Evolution of allelic dimorphism in malarial surface antigens

Cited by 32 publications

References 28 publications

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Molecular markers and genetic diversity of Plasmodium vivax

Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum

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