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1. Supplement 5 Intron positions in the highly conserved kinase domains of metazoan receptor tyrosine kinases are not related to intron positions in the choanoflagellate RTK nor in the serine-threonine kinase, PKC. In FGFRs and related receptor tyrosine kinases ancestral introns are positioned at the boundaries of eleven subdomains identified by Hanks et al., 1988 in RTK as well as serine-threonine kinases. Included are in the alignment with superimposed intron positions FGFRs, Ret tyrosine kinase and VEGFR, which originate from a common ancestor (Coulier et al., 1997). In contrast, although the eleven subdomains are clearly recognizable, no such pattern exists in the „compound“ Monosiga tyrosine kinase, which has been included as most ancestral tyrosine kinase known to date. Outside the receptor tyrosine kinase family, represented here by human PKCb, the fungal Cryoptococcus PKC as well as a Cryoptococcus tyrosine/threonine kinase, introns are not positioned like in the FGFRs. The intron-exon pattern in metazoan receptor tyrosine kinases thus seems to have evolved independently from the other kinases included in this figure.

2. I II 8 III IV 9 V VIa 10 VIb VII 11 VIII 12 IX 13 X 14 XI 15