Molecular markers and genetic diversity of Plasmodium vivax

Abstract

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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