Supplement 6. Evolutionary relationships of 27 kinases used in this study The evolutionary history was inferred using the Neighbor-Joining method [1]. The optimal tree with the sum of branch length = 7.29114517 is shown. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (5000 replicates) are shown next to the branches [2]. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the Poisson correction method [3] and are in the units of the number of amino acid substitutions per site. All positions containing gaps and missing data were eliminated from the dataset (Complete Deletion option). There were a total of 228 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4 [4].

1. Saitou N & Nei M (1987) The neighbor-joining method: A new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4:406-425.2. Felsenstein J (1985) Confidence limits on phylogenies: An approach using the bootstrap. Evolution 39:783-791.3. Zuckerkandl E & Pauling L (1965) Evolutionary divergence and convergence in proteins, pp. 97-166 in Evolving Genes and Proteins, edited by V. Bryson and H.J. Vogel. Academic Press, New York.4. Tamura K, Dudley J, Nei M & Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Molecular Biology and Evolution 24:1596-1599.

Hs 2

Hs 3

Hs 1

Hs 4

Sk b

Sp

Sk a

Ci

Nv a

Hv

Nv b

Cc c

Lg

Cc b

Cc a

Cc d

Tc

Dm btl

Dm htl

Ce

Hs VEGFR

Ta kin

Hs RET

Mb kin

Cn TK

Cn PKC

Hs PKCb99

99

99

5797

99

49

95

4092

49

4083

28

48

78

4836

19

12

43

9

5

7

0.1

Ta

Mb RTK