A Plasmodium Whole-Genome Synteny Map: Indels and Synteny Breakpoints as Foci for Species-Specific Genes

Abstract

Whole-genome comparisons are highly informative regarding genome evolution and can reveal the conservation of genome organization and gene content, gene regulatory elements, and presence of species-specific genes. Initial comparative genome analyses of the human malaria parasite Plasmodium falciparum and rodent malaria parasites (RMPs) revealed a core set of 4,500 Plasmodium orthologs located in the highly syntenic central regions of the chromosomes that sharply defined the boundaries of the variable subtelomeric regions. We used composite RMP contigs, based on partial DNA sequences of three RMPs, to generate a whole-genome synteny map of P. falciparum and the RMPs. The core regions of the 14 chromosomes of P. falciparum and the RMPs are organized in 36 synteny blocks, representing groups of genes that have been stably inherited since these malaria species diverged, but whose relative organization has altered as a result of a predicted minimum of 15 recombination events. P. falciparum-specific genes and gene families are found in the variable subtelomeric regions (575 genes), at synteny breakpoints (42 genes), and as intrasyntenic indels (126 genes). Of the 168 non-subtelomeric P. falciparum genes, including two newly discovered gene families, 68% are predicted to be exported to the surface of the blood stage parasite or infected erythrocyte. Chromosomal rearrangements are implicated in the generation and dispersal of P. falciparum-specific gene families, including one encoding receptor-associated protein kinases. The data show that both synteny breakpoints and intrasyntenic indels can be foci for species-specific genes with a predicted role in host-parasite interactions and suggest that, besides rearrangements in the subtelomeric regions, chromosomal rearrangements may also be involved in the generation of species-specific gene families. A majority of these genes are expressed in blood stages, suggesting that the vertebrate host exerts a greater selective pressure than the mosquito vector, resulting in the acquisition of diversity. Malaria, caused by the parasite Plasmodium falciparum, is one of the most devastating infectious diseases. Rodent malaria parasites (RMPs), such as P. berghei, P. chabaudi, and P. yoelii, are used as models for P. falciparum. For the use of these models in studies of human disease, insight into both the similarities and differences in the genomics and biology of these parasites is important. The availability of significant but partial genome data of the RMPs enabled the construction of a virtual composite RMP genome and its comparison with the P. falciparum genome, generating a so-called synteny map. Analysis of this map provided the desired comparative insights. A high level of conservation exists between roughly 85% of the genes at the level of content and order, but 168 P. falciparum-specific genes that disrupted the conserved genome segments were identified. The majority of these genes were predicted to play a role in host–parasite interactions. This study indicates that determination of the synteny breakpoints may help to rapidly identify the species-specific gene content of future Plasmodium genomes, providing the malaria research community with a powerful investigative tool. The findings may also be of interest to those studying chromosomal evolution.