Comparative DNA sequence analysis of mouse and human protocadherin gene clusters
Comparative DNA sequence analysis of mouse and human protocadherin gene clusters
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DOI：
10.1101/gr.167301
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发表时间：
2001-03-01
期刊：
影响因子：
7
通讯作者：
Maniatis, T
中科院分区：
文献类型：
--
作者：
Wu, Q;Zhang, T;Maniatis, T
人类原钙粘蛋白α、β和γ基因簇（命名为Pcdh α [基因符号PCDHA]、Pcdh β [PCDHB]和Pcdh γ [PCDHG]）的基因组结构与免疫球蛋白和T细胞受体基因的基因组结构非常相似。每种原钙粘蛋白的细胞外和跨膜结构域由一个异常大的“可变”区外显子编码，而细胞内结构域由位于可变区外显子串联阵列下游的三个小的“恒定”区外显子编码。在这里，我们报告的结果比较DNA序列分析的orthopathic人（750 kb）和小鼠（900 kb）原钙粘蛋白基因簇。Pcdh α和Pcdh γ基因簇在两个物种中的组织几乎是相同的，而小鼠Pcdh β基因簇比人类Pcdh β基因簇更大，包含更多的基因。我们鉴定了可变区外显子上游的保守DNA序列，发现这些序列在直系同源物之间比在旁系同源物之间更保守。在该区域内，存在高度保守的DNA序列基序，其位于每个可变区外显子的翻译起始密码子上游的大约相同位置处。此外，每个基因簇的可变区含有丰富的CpG岛阵列，其位置对应于每个可变区外显子的位置。这些观察结果与每个可变区外显子的表达由不同的启动子调节的提议一致，该启动子在小鼠和人的正向可变区外显子之间高度保守。
The genomic organization of the human protocadherin alpha, beta, and gamma gene clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell receptor genes. The extracellular and transmembrane domains of each protocadherin protein are encoded by an unusually large "variable" region exon, while the intracellular domains are encoded by three small "constant" region exons located downstream from a tandem array of variable region exons. Here we report the results of a comparative DNA sequence analysis of the orthologous human (750 kb) and mouse (900 kb) protocadherin gene clusters. The organization of Pcdh alpha and Pcdh gamma gene clusters in the two species is virtually identical, whereas the mouse Pcdh beta gene cluster is larger and contains more genes than the human Pcdh beta gene cluster. We identified conserved DNA sequences upstream of the variable region exons, and found that these sequences are more conserved between orthologs than between paralogs. Within this region, there is a highly conserved DNA sequence motif located at about the same position upstream of the translation start codon of each variable region exon. In addition, the variable region of each gene cluster contains a rich array of CpG islands, whose location corresponds to the position of each variable region exon. These observations are consistent with the proposal that the expression of each variable region exon is regulated by a distinct promoter, which is highly conserved between orthologous variable region exons in mouse and human.