Classification and Evolution of Supergene Families Based on Molecular Phylogenetic Tree

免疫球蛋白（IG）-、纤连蛋白III型（FN-III）-和钙粘蛋白-相关序列通常在细胞粘附分子的细胞外区域的多个重复中发现。比较了钙粘蛋白超家族13个已知成员的82个不同钙粘蛋白样重复序列的6个高度保守区域的氨基酸序列，并基于比对计算了表示为氨基酸与位置矩阵的频率矩阵。使用频率矩阵，在蛋白质数据库中搜索钙粘蛋白超家族的其他成员。结果发现，ret蛋白，受体蛋白酪氨酸激酶，含有钙粘蛋白样重复的细胞外区域。对FN-III超家族也进行了类似的分析。9种受体蛋白酪氨酸激酶显示出与已知的FN-III样重复序列在序列上具有显著的相似性。已经报道了几种受体蛋白酪氨酸激酶在其胞外区具有Ig样重复序列。因此，这些受体蛋白酪氨酸激酶，连同其结构尚未被表征的其余受体，可以基于胞外结构域的结构差异被分类为至少四个不同的组。这种分类也支持从进化的观点：从共享的激酶结构域推断的分子系统发育树揭示了树中的分支模式和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.