Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

Abstract

Malaria, one of the most serious infectious diseases prevalent in the tropics, is caused by the genus Plasmodium. Despite considerable global efforts to control this parasitic disease at least 90% of deaths still occur in sub-Saharan Africa (WHO, 2010). The rising threat of drugresistant parasites, together with key interventions dependent on the use of a limited class of insecticides, underscore the fragility of malaria control. A better understanding of the parasite biology is required to gain insights for cost-effective tools or strategies including malaria vaccines and new antimalarial drugs that can be instrumental for sustained control, if not elimination, of malaria. Malaria parasites comprise a diverse group of over 200 Plasmodium species that infect mammals, birds and reptiles (Levine, 1988). Each Plasmodium species exhibits a restricted host range, such that primate parasite cannot infect rodent, bird or reptile hosts. To find genomic factors that determine host range transcends the interest of malaria researchers. It is essential for control and conservation of wildlife. Recently, genome projects on several Plasmodium species from different hosts have been completed (Gardner et al., 2002; Carlton et al., 2002, 2008; Pain et al., 2008), with gene information available in the public database (http://plasmodb.org/plasmo/). By comparing the genomes from different species we obtain basic information at the molecular level on how Plasmodium has evolved and allows us to infer the function of genes and noncoding regions in the genome. One of the prominent features of Plasmodium genomes is the presence of various unique multigene families. Multigene families are a group of related genes that are presumed to share a common ancestor and are derived from each other by duplication and subsequent divergence. One such example, the largest family identified so far in human, primate and rodent malaria, is the Plasmodium interspersed repeat, pir (Janssen et al., 2004). The pir gene family members are highly species-specific, suggesting evolution of lineage-specific immune evasion mechanisms. P. falciparum var gene family is by far the best documented multigene family of the most virulent human malaria parasite. Products of var genes appear on the surface of infected erythrocytes and are involved in antigenic variation to evade host immunity. Other species-specific gene families encode proteins involved in host cell invasion, e.g. rhoptry proteins and parasite surface antigens, merozoite surface protein-3 and -7. There are also examples of families with few gene members. In sharp contrast to several hundreds of tandem arrayed rRNA gene family members in other eukaryotes,