The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites

Abstract

The genus Plasmodium is a diversified group of parasites with more than 200 known species that includes those causing malaria in humans. These parasites use numerous proteins in a complex process that allows them to invade the red blood cells of their vertebrate hosts. Many of those proteins are part of multi-gene families; one of which is the merozoite surface protein-3 (msp3) family. The msp3 multi-gene family is considered important in the two main human parasites, Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously expressed in the blood stage (merozoite) and are immunogenic. There are large differences among Plasmodium species in the number of paralogs in this family. Such differences have been previously explained, in part, as adaptations that allow the different Plasmodium species to invade their hosts. To investigate this, we characterized the array containing msp3 genes among several Plasmodium species, including P. falciparum and P. vivax. We first found no evidence indicating that the msp3 family of P. falciparum was homologous to that of P. vivax. Subsequently, by focusing on the diverse clade of nonhuman primate parasites to which P. vivax is closely related, where homology was evident, we found no evidence indicating that the interspecies variation in the number of paralogs was an adaptation related to changes in host range or host switches. Overall, we hypothesize that the evolution of the msp3 family in P. vivax is consistent with a model of multi-allelic diversifying selection where the paralogs may have functionally redundant roles in terms of increasing antigenic diversity. Thus, we suggest that the expressed MSP3 proteins could serve as “decoys”, via antigenic diversity, during the critical process of invading the host red blood cells.

Evolution of the merozoite surface protein 7 ( msp7 ) family in Plasmodium vivax and P . falciparum : A comparative approach

“…: P. vivax, P. cynomolgi, P. inui ; see Fig. S2), thus msp7 differs from Pvmsp3 and its orthologs in non-human primates (Rice et al, 2014). However, as in Pvmsp3 (Rice et al, 2014), there is sequence length polymorphism in many msp7 paralogs in the P. vivax clade among different isolates within species (Fig.…”

“…Multigene families in Plasmodium harbor extraordinary variation to the extent that it is difficult to identify clear orthologs even in closely related species (Frech and Chen, 2011; Neasfy et al, 2012; Rice et al, 2014). In the case of msp7 , orthologs are identifiable across species but they have diverged enough to hamper our ability to describe evolutionary processes at the genus level.…”

“…In contrast, the msp3 genes in P. vivax ( Pvmsp3 ) and their orthologs from related species parasitizing non-human primates in Southeast Asia, are not orthologs to those identified as the Pfmsp3 family in P. falciparum and its related species (Rice et al, 2014). This leaves msp7 as the only MSP gene family, with a role in erythrocyte invasion, found across all the known primate and rodent malarial parasites (Boyle et al, 2014).…”

The utility of genomic data forPlasmodium vivaxpopulation surveillance

“…These include antigens involved in the binding and invasion of host cells, 6,54 potential vaccine candidates, 55 and loci associated with drug resistance. 26 Initial comparisons of P. vivax genomes have found high levels of variation in many of the antigens involved in red blood cell invasion, 19 and even suggestions of common copy number variation in antigen families such as vir and MSP3.…”

“…26 Initial comparisons of P. vivax genomes have found high levels of variation in many of the antigens involved in red blood cell invasion, 19 and even suggestions of common copy number variation in antigen families such as vir and MSP3. 54 This indicates that different subpopulations of P. vivax could present very different antigenic sequences and even have different repertoires of antigens, with clear relevance for immunity and vaccine development. Additionally, genome wide screens for genes with a pattern of polymorphism consistent with the action of natural selection have identified new loci that are of interest in understanding P. vivax invasion biology.…”