Hughes A L
Department of Biology, Pennsylvania State University, University Park 16802, USA.
J Mol Evol. 1996 Feb;42(2):247-56. doi: 10.1007/BF02198851.
A phylogenetic analysis of src-related protein tyrosine kinases (PTKs) showed that one group of these genes is quite ancient in the animals, its divergence predating the divergence of the diploblast and triploblast phyla. Three other major groupings of genes were found to predate the divergence of protostome and deuterostome phyla. Most known src-related PTKs of mammals were found to belong to five well-differentiated families: srcA, srcB, abl, csk, and tec. One srcA gene (fyn) has an alternatively spliced seventh exon which shows a different pattern of relationship from the remainder of the gene; this suggests that this exon may have been derived by a recombinational event with another gene, perhaps one related to fgr. The recently published claim that mammalian members of this family expressed in the nervous system evolve more slowly at nonsynonymous nucleotide sites than do those expressed in the immune system was not supported by an analysis of 13 pairs of human and mouse orthologues. Rather, T-cell-specific src-related PTKs were found to have higher rates of nonsynonymous substitution than were those having broader expression. This effect was particularly marked in the peptide binding site of the SH2 domain. While the SH2 binding site was highly conserved among paralogous mammalian members of the srcA and srcB subfamilies, no such effect was seen in the comparison of paralogous members of the csk and tec subfamilies. This suggests that, while the peptide binding function of SH2 is conserved within both srcA and srcB subfamilies, paralogous members of the csk and tec subfamilies have diverged functionally with respect to peptide recognition by SH2.
对src相关蛋白酪氨酸激酶（PTK）进行的系统发育分析表明，这些基因中的一组在动物中相当古老，其分化早于双胚层和三胚层动物门的分化。另外三个主要的基因分组被发现早于原口动物和后口动物门的分化。哺乳动物中大多数已知的src相关PTK属于五个分化良好的家族：srcA、srcB、abl、csk和tec。一个srcA基因（fyn）有一个选择性剪接的第七外显子，其与基因其余部分的关系模式不同；这表明该外显子可能是通过与另一个基因的重组事件产生的，也许是一个与fgr相关的基因。最近发表的一项声明称，在神经系统中表达的该家族哺乳动物成员在非同义核苷酸位点的进化速度比在免疫系统中表达的成员慢，但对13对人和小鼠直系同源基因的分析并不支持这一观点。相反，发现T细胞特异性src相关PTK的非同义替换率高于表达范围更广的PTK。这种效应在SH2结构域的肽结合位点尤为明显。虽然SH2结合位点在srcA和srcB亚家族的同源哺乳动物成员中高度保守，但在csk和tec亚家族的同源成员比较中未观察到这种效应。这表明，虽然SH2的肽结合功能在srcA和srcB亚家族中都是保守的，但csk和tec亚家族的同源成员在SH2对肽的识别功能方面已经发生了分化。
