Cetkovic Helena, Grebenjuk Vladislav A, Müller Werner E G, Gamulin Vera
Department of Molecular Biology, Rudjer Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia.
Gene. 2004 Nov 24;342(2):251-61. doi: 10.1016/j.gene.2004.07.044.
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., Caenorhabditis elegans or Drosophila melanogaster (two in each). Three proteins, SRC1SD, SRC2SD and SRC3SD, were fully characterized. The overall homology (identity+similarity) among the three 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 tags (ESTs) 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 six and src2SD gene only one 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.
海洋海绵Suberites domuncula是最古老、最简单的后生动物门多孔动物门的成员，其基因组编码至少五个Src型蛋白基因，比秀丽隐杆线虫或果蝇（各两个）要多。对三种蛋白SRC1SD、SRC2SD和SRC3SD进行了全面表征。三种Suberites domuncula Src蛋白之间的总体同源性（同一性+相似性）（68 - 71%）远低于淡水海绵直系同源Src蛋白之间的序列保守性（82 - 85%）。因此，很可能在假想的后生动物祖先原后生动物的基因组中已经存在多个src基因/蛋白。我们在Suberites domuncula表达序列标签（EST）数据库中鉴定出了与蛋白酪氨酸激酶（PTK）无关的其他Src同源2（SH2）和3（SH3）结构域。来自不同物种的与Src相关的SH2和SH3结构域比同一生物体（Suberites domuncula）中不同蛋白的SH2和SH3结构域保守得多，这支持了这样一种观点，即共同的祖先src基因已经是一种由SH3、SH2和酪氨酸激酶（TK）结构域组成的多结构域蛋白。对两个Suberites domuncula src基因进行了全序列测定：src1SD基因有六个内含子，src2SD基因在SH2结构域之前只有一个内含子，且位于两个基因的相同位置。从鱼类到人类的所有脊椎动物src基因都起源于同一个祖先基因，因为它们在保守位置都有10个内含子。然而，无脊椎动物中的src基因内含子较少且位置不同。只有SH2结构域之前的内含子在所有已知src基因中处于绝对保守的位置（和相位），这表明至少这个内含子已经存在于所有后生动物共同的祖先基因中。我们的结果还表明，这个祖先src中的TK结构域由单个外显子编码。
