Abstract
Rodent malaria parasites (RMP) are used extensively as models of human malaria. Draft RMP genomes have been published for Plasmodium yoelii, P. berghei ANKA (PbA) and P. chabaudi AS (PcAS). Although availability of these genomes made a significant impact on recent malaria research, these genomes were highly fragmented and were annotated with little manual curation. The fragmented nature of the genomes has hampered genome wide analysis of Plasmodium gene regulation and function. We have greatly improved the genome assemblies of PbA and PcAS, newly sequenced the virulent parasite P. yoelii YM genome, sequenced additional RMP isolates/lines and have characterized genotypic diversity within RMP species. We have produced RNA-seq data and utilised it to improve gene-model prediction and to provide quantitative, genome-wide, data on gene expression. Comparison of the RMP genomes with the genome of the human malaria parasite P. falciparum and RNA-seq mapping permitted gene annotation at base-pair resolution. Full-length chromosomal annotation permitted a comprehensive classification of all subtelomeric multigene families including the `Plasmodium interspersed repeat genes' (pir). Phylogenetic classification of the pir family, combined with pir expression patterns, indicates functional diversification within this family. Complete RMP genomes, RNA-seq and genotypic diversity data are excellent and important resources for gene-function and post-genomic analyses and to better interrogate Plasmodium biology. Genotypic diversity between P. chabaudi isolates makes this species an excellent parasite to study genotype-phenotype relationships. The improved classification of multigene families will enhance studies on the role of (variant) exported proteins in virulence and immune evasion/modulation.
Highlights
Rodent malaria parasites (RMP) are used extensively as models of human malaria
More than 98% of the predicted genes are present as full-length gene models and we were able to ascribe putative functions to 56% to 61% of these
The RMP reference genomes have a size of 18.5 to 21.9 Mb (Table 1), confirming the smaller genome sizes of RMPs compared with primate malaria species but both the mitochondrial and apicoplast RMP genomes are highly comparable in size and gene content to those of P. falciparum (Table 1)
Summary
Rodent malaria parasites (RMP) are used extensively as models of human malaria. Draft RMP genomes have been published for Plasmodium yoelii, P. berghei ANKA (PbA) and P. chabaudi AS (PcAS). The availability of efficient reverse genetics technologies for P. berghei and P. yoelii [9,10,11] and the ability to analyse these parasites throughout the complete life cycle have made these two species the preferred models for analysis of Plasmodium gene function [12,13,14]. For these two species more than 600 different genetically modified mutants have been reported [15]
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