Classification and Evolution of Supergene Families Based on Molecular Phylogenetic Tree

免疫球蛋白(Ig)-、纤维连接蛋白i型(FN-Ill)-和钙链蛋白相关序列经常在细胞粘附分子的细胞外区域出现多个重复序列。比较了13个已知cadhefin超家族成员的82个cadherin样重复序列在6个高度保守区域的氨基酸序列，并基于比对计算了以氨基酸-位置矩阵表示的频率矩阵。利用频率矩阵，在蛋白质数据库中进一步搜索cadhefin超家族成员。发现ret蛋白是一种酪氨酸激酶受体蛋白，在细胞外区域含有钙粘蛋白样重复序列。FN-Ill超家族也进行了类似的分析。九种受体蛋白酪氨酸激酶在序列上与已知的fn - ill样重复序列有显著的相似性。一些受体蛋白酪氨酸激酶已经被报道在其细胞外区域有类似igg的重复序列。因此，这些受体蛋白酪氨酸激酶，连同其余的结构尚未确定的受体，可以根据细胞外结构域的结构差异，至少分为四个不同的组。这种分类也得到了进化观点的支持：从共享激酶结构域推断出的分子系统发育树揭示了树中的分支模式与基于结构差异的分组之间的密切关系。

Immunoglobulin(Ig)-, fibronectin type Ill(FN-Ill)-, and cadhefin-related sequences are often found in multiple repeats in the extracellular regions of cell adhesion molecules. The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadhefin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment. Using the frequency matrix, further members of the cadhefin superfamily were searched in protein database. It was found that the ret protein, a receptor protein tyrosine kinase, contains cadherin-like repeats in the extracellular region. A similar analysis was also carried out for the FN-Ill superfamily. Nine receptor protein tyrosine kinases were shown to exhibit significant similarities in sequence with known FN-Ill-like repeats. Several receptor protein tyrosine kinases have already been reported to have Ig-like repeats in their extracellular regions. Thus these receptor protein tyrosine kinases, together with the remaining receptors whose structures are not yet characterized, are possible to be classified into at least four distinct groups based on the structural differences in the extracellular domains. This classification was also supported from an evolutional viewpoint : A molecular phylogenetic tree inferred from the shared kinase domains revealed a close relationship between the branching patterns in tree and the grouping based on the structural differences.