Gene conversion and the evolution of protocadherin gene cluster diversity
Gene conversion and the evolution of protocadherin gene cluster diversity
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DOI：
10.1101/gr.2133704
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发表时间：
2004-03-01
期刊：
影响因子：
7
通讯作者：
Myers, RM
中科院分区：
文献类型：
--
作者：
Noonan, JP;Grimwood, J;Myers, RM
由原钙粘蛋白基因簇编码的突触细胞粘附分子被假设为提供参与发育中大脑中突触复杂性产生的分子密码。原钙粘蛋白簇基因的拷贝数和序列含量在脊椎动物种间的变异可能反映了原钙粘蛋白功能的适应性差异。我们已经完成了斑马鱼原钙粘蛋白簇基因的全序列分析。斑马鱼有两个未连接的原钙粘蛋白簇，DrPcdh 1和DrPcdh 2。与哺乳动物原钙粘蛋白簇一样，DrPcdhl具有α和γ可变区和恒定区外显子。在哺乳动物中鉴定的共有原钙粘蛋白启动子基序序列在斑马鱼中也是保守的。然而，斑马鱼和哺乳动物的原钙粘蛋白之间几乎没有明显的同源关系。在这里，我们表明，原钙粘蛋白簇基因在人类，小鼠，大鼠和斑马鱼是受惊人的基因转换事件。这些事件限于编码序列的区域，特别是胞外域6和胞质结构域的编码序列。旁系同源物之间的多样性仅限于排除在转换事件之外的特定胞外域。转换事件也与第三位GC含量的增加密切相关。我们提出，在多样化的胞外结构域的谱系特异性复制，限制基因转换和适应性变异的组合驱动脊椎动物原钙粘蛋白簇的进化。
The synaptic cell adhesion molecules encoded by the protocadherin gene Cluster are hypothesized to provide a molecular code involved in the generation of synaptic complexity ill the developing brain. Variation ill COPY number and sequence content of protocadherin cluster genes among vertebrate species Could reflect adaptive differences in protocadherin function. We have completed ail analysis of zebrafish protocadherin cluster genes. Zebrafish have two unlinked protocadherin Clusters, DrPcdhl and DrPcdh2. Like mammalian protocadherin Clusters, DrPcdhl has both alpha and gamma variable and constant region exons. A consensus protocadherin promoter motif sequence identified ill mammals is also conserved ill zebrafish. Few orthologous relationships, however, are apparent between zebrafish and mammalian protocadherin proteins. Here we show that protocadherin Cluster genes ill human, mouse, rat, and zebrafish are Subject to striking gene conversion events. These events are restricted to regions of the coding sequence, particularly the coding sequences of ectodomain 6 and the cytoplasmic domain. Diversity among paralogs is restricted to particular ectodomains that are excluded from conversion events. Conversion events are also strongly correlated with an increase in third-position GC content. We propose that the combination of lineage-specific duplication, restricted gene conversion, and adaptive variation in diversified ectodomains drives vertebrate protocadherin cluster evolution.