Comparative genomics of cryptosporidium

Abstract

Until recently, the apicomplexan parasites, Cryptosporidium hominis and C. parvum, were considered the same species. However, the two parasites, now considered distinct species, exhibit significant differences in host range, infectivity, and pathogenicity, and their sequenced genomes exhibit only 95-97% identity. The availability of the complete genome sequences of these organisms provides the potential to identify the genetic variations that are responsible for the phenotypic differences between the two parasites. We compared the genome organization and structure, gene composition, the metabolic and other pathways, and the local sequence identity between the genes of these two Cryptosporidium species. Our observations show that the phenotypic differences between C. hominis and C. parvum are not due to gross genome rearrangements, structural alterations, gene deletions or insertions, metabolic capabilities, or other obvious genomic alterations. Rather, the results indicate that these genomes exhibit a remarkable structural and compositional conservation and suggest that the phenotypic differences observed are due to subtle variations in the sequences of proteins that act at the interface between the parasite and its host.

Figure 1

Pathway scores (excerpt). Completeness, connectedness, and support scores of the inferred metabolic pathways of C. hominis and C. parvum, along with nine other apicomplexans and an external reference (Saccharomyces cerevisiae). The three scores are represented as follows. The color of the circles reflects the support, from white (support of 0) to blue (maximal support). The size of each circle is proportional to the completeness; that is, the larger the circle, the more complete the pathway (see text). The color of the wedge—available for metabolic pathways only—reflects the connectedness, from red (connectedness of 0) to green (connectedness of 100%). Species are clustered according to their completeness score. Pathways are ranked by decreasing power to discriminate between the Cryptosporidium and the other apicomplexans. Only the 25 most discriminative pathways are shown; a complete figure is available as Supplementary Figure 3. All score values are available in Supplementary Table 2.

Figure 2

Protein localization and selective pressure. Association between protein localization and selective pressure. Abscissa: cutoffs used for the identification of positively selected proteins (are considered as positively selected proteins with dN/dS ratios higher than or equal to the cutoff). Ordinate: enrichment (triangles) and P value (circles) of the set of positively selected proteins for a given localization—either cytoplasmic, membrane-bound, or secreted.