Classification and Evolution of Supergene Families Based on Molecular Phylogenetic Tree

免疫球蛋白(Ig)、纤维连接蛋白Ill(Fn-Ill)和钙粘蛋白相关序列常在细胞黏附分子胞外区的多个重复序列中被发现。比较了13个钙粘连蛋白超家族成员的82个不同的类钙粘蛋白重复序列的6个高度保守区的氨基酸序列，并根据比对结果计算了以氨基酸-位置矩阵表示的频率矩阵。利用频率矩阵，在蛋白质数据库中搜索到更多的钙粘蛋白超家族成员。研究发现，Rit蛋白是一种受体蛋白酪氨酸激酶，在胞外区含有类钙粘素重复序列。对FN-Ill超家族也进行了类似的分析。9个受体蛋白酪氨酸激酶的序列与已知的Fn-Ill样重复序列显示出显著的相似性。一些受体蛋白酪氨酸激酶已经被报道在它们的胞外区有Ig样重复。因此，根据细胞外域的结构差异，这些受体蛋白酪氨酸激酶，以及结构尚未确定的其余受体，可能被分为至少四个不同的组。这一分类也从进化的角度得到了支持：从共享的激酶结构域推导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.