An evolutionary perspective on the kinome of malaria parasites

Abstract

Malaria parasites belong to an ancient lineage that diverged very early from the main branch of eukaryotes. The approximately 90-member plasmodial kinome includes a majority of eukaryotic protein kinases that clearly cluster within the AGC, CMGC, TKL, CaMK and CK1 groups found in yeast, plants and mammals, testifying to the ancient ancestry of these families. However, several hundred millions years of independent evolution, and the specific pressures brought about by first a photosynthetic and then a parasitic lifestyle, led to the emergence of unique features in the plasmodial kinome. These include taxon-restricted kinase families, and unique peculiarities of individual enzymes even when they have homologues in other eukaryotes. Here, we merge essential aspects of all three malaria-related communications that were presented at the Evolution of Protein Phosphorylation meeting, and propose an integrated discussion of the specific features of the parasite's kinome and phosphoproteome.

Figure 1.

Taxonomic arrangement of Plasmodium and model organisms on the eukaryotic tree. Cladogram of representative species in Eukaryota, with Plasmodium and humans indicated in bold. Colours indicate the eukaryotic supergroups defined by Adl et al. [7]. Rhizaria and Chromalveolata are placed together per Hackett et al. [8], and the phylogeny of apicomplexan species is according to Kuo et al. [9]. The tree image was rendered with the Interactive Tree of Life server (iTOL) [10] and edited in Inkscape (http://inkscape.org).

Figure 2.

Phylogenetic tree of the Plasmodium falciparum kinome. Circular tree of all 91 eukaryotic protein kinases (ePK) in P. falciparum as defined by Talevich et al. [24]. Representative genes from human (Hs), Arabidopsis thaliana (At) and Plasmodium berghei (Pb) are indicated with labels coloured gold, green and purple, respectively. Branch and arc colours indicate kinase classification by ePK major group [25,26], according to Talevich et al. [24], with minor modifications in group assignment according to the gene tree. To construct the tree, the sequences of 91 protein kinases were retrieved from GeneDB (http://genedb.org), P. falciparum 3D7 sequence v. 3. Conserved regions of the kinase domain were aligned with MAPGAPS [27] and unconserved sequence positions, as identified by MAPGAPS, were removed. A gene tree was then inferred from the resulting 245-column alignment using RAxML [28] with the rapid bootstrap analysis and maximum-likelihood tree search algorithm, LG amino acid substitution model, and gamma model of substitution rate heterogeneity. The tree image was rendered with the Interactive Tree of Life server (iTOL) [10] and edited in Inkscape (http://inkscape.org). A grey circle on a branch indicates bootstrap support greater than 50; larger circles indicate greater bootstrap values.

Figure 3.

ePK group distribution across representative of the main eukaryotic taxons. Composition of protein kinase major groups and the apicomplexan-specific FIKK family in the genomes of three Plasmodium species and three other apicomplexans. The kinomes of the model organisms Saccharomyces cerevisiae (Baker's yeast), Drosophila melanogaster (fruitfly) and Homo sapiens (human), as well as the phylogenetically distant parasite Giardia lamblia (figure 1) and the microsporidium Encephalitozoon cuniculi, which has the smallest characterized eukaryotic kinome [35], are included for comparison. The cladogram along the left edge indicates the evolutionary relationships between species. In the stacked bar chart associated with each species, block width indicates number of genes found belonging to each major group of eukaryotic protein kinases; total bar width indicates total kinome size. Data are adapted from Talevich et al. [24] and KinBase (http://kinase.com/kinbase/).