Comparative Kinomics

A great deal can be learned about the evolution of the protein kinase superfamily through the comparison of the kinomes of different eukaryotes [7,8] (Figures 1 and 2). Fifty one protein kinase families are common to all eukary-otes; these serve cell essential functions; examples are Cdk, CAMK, PKA, MAP kinase, etc. Interestingly, most of the atypical protein kinase families exist in all four kinomes yeasts, but clearly were not selected for diversification during evolution. Seven families are unique to the budding and fission yeasts. These have functions commensurate with a fungal life style, such as cell wall biosynthesis and stress responses.

Among the metazoan kinomes analyzed to date there are 93 families in common, which presumably were present in the last common ancestor of nematodes, flies and vertebrates.

Figure 1 Occurrence of protein kinase families and subfamilies in the budding yeast, nematode, fly and human genomes illustrated by a Venn diagram. Comparison of 'orthology groups' across large evolutionary distances shows 51 distinct families/subfamilies conserved between all 4 kinomes, and 93 more in all three metazoan kinomes.

Figure 1 Occurrence of protein kinase families and subfamilies in the budding yeast, nematode, fly and human genomes illustrated by a Venn diagram. Comparison of 'orthology groups' across large evolutionary distances shows 51 distinct families/subfamilies conserved between all 4 kinomes, and 93 more in all three metazoan kinomes.

Figure 2 Trikinome dendrogram depicting the distribution of tyrosine kinases in nematode, fly and human. Most tyrosine kinases fall into distinct families (labeled), some of which are expanded greatly in worm (Fer, Kin6, Kin16), others in human (Eph, Src). As for other kinase groups, there are no significant expansions in fly. Of 30 tyrosine kinase families, 14 are present in all three genomes. Vertebrate-specific families include Tie, Axl and Lmr; coelomate-specific families (fly+human) are Jak, Syk, Tek, CCK4, MuSK, Ret, Sev and PDGFR/ VEGRFR, while Met and Trk are present in worm and human but not fly.

Figure 2 Trikinome dendrogram depicting the distribution of tyrosine kinases in nematode, fly and human. Most tyrosine kinases fall into distinct families (labeled), some of which are expanded greatly in worm (Fer, Kin6, Kin16), others in human (Eph, Src). As for other kinase groups, there are no significant expansions in fly. Of 30 tyrosine kinase families, 14 are present in all three genomes. Vertebrate-specific families include Tie, Axl and Lmr; coelomate-specific families (fly+human) are Jak, Syk, Tek, CCK4, MuSK, Ret, Sev and PDGFR/ VEGRFR, while Met and Trk are present in worm and human but not fly.

Interestingly, the flowering plant Arabidopsis thaliana, with ~25,500 genes, is predicted to have 1085 protein kinase genes [12], which is a significantly higher percentage of total genes (4%) than in vertebrates. None of the plant protein kinases belong to the tyrosine kinase family, and the greater number of protein kinases is in part accounted for by large families, several of which are unique to plants, such as a leucine-rich repeat (LRR) receptor serine kinases, which act as receptors for fungal pathogens and other environmental agents, and the calcium-dependent protein kinases (CDPK) (http://plantsp.sdsc.edu/). In addition, a partial genomic duplication in Arabidopsis may also contribute to the large number of protein kinase genes [13]. However, the total number of protein kinase genes in rice appears to be similar. The ability to respond rapidly and appropriately to ones external environment is obviously particularly important in sessile organisms like plants, and this selection pressure could account for the development and expansion of these new families of protein kinase.

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