engleski

Src Proteins/src genes: from sponges to mammals

The genome of marine sponge Suberites domuncula, a member of the most ancient and most simple metazoan phylum – Porifera, encodes at least five genes for Src type proteins, more than i.e. C. elegans or D. melanogaster (2 in each). Three proteins, SRC1SD, SRC2SD and SRC3SD were fully characterized. The overall homology (identity+similarity) among the 3 S. domuncula Srcs (68-71%) is much lower than the sequence conservation between orthologous Src proteins from freshwater sponges (82-85%). It is therefore very likely that several src genes/proteins were already present in the genome of Urmetazoa, the hypothetical metazoan ancestor. We have identified in the S. domuncula expressed sequence tag (EST) database further Src homology 2 (SH2) and 3 (SH3) domains that are unrelated to protein tyrosine kinases (PTKs). Src-related SH2 and SH3 domains from different species are much more conserved than SH2 and SH3 domains from different proteins in the same organism (S. domuncula), supporting the view that the common, ancestral src gene was already a multidomain protein composed of SH3, SH2 and tyrosine kinase (TK) domains. Two S. domuncula src genes were fully sequenced: src1SD gene has 6 and src2SD gene only 1 intron in front of SH2 domain, located at the same position in both genes. All vertebrate src genes, from fish to human, originated from the same ancestral gene, because they all have 10 introns at conserved positions. However, src genes in invertebrates have fewer introns that are located at different positions. Only the intron in front of the SH2 domain is present at the absolutely conserved position (and phase) in all known src genes, indicating that at least this intron was already present in the ancestral gene, common to all Metazoa. Our results also suggest that TK domain in this ancestral src was encoded on a single exon.

Src-family kinases; evolution; Porifera; introns; SH3 domain; SH2 domain

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