Linnenbach A J, Seng B A, Wu S, Robbins S, Scollon M, Pyrc J J, Druck T, Huebner K
Wistar Institute, Philadelphia, Pennsylvania 19104.
Mol Cell Biol. 1993 Mar;13(3):1507-15. doi: 10.1128/mcb.13.3.1507-1515.1993.
The gene encoding the carcinoma-associated antigen defined by the monoclonal antibody GA733 is a member of a family of at least two type I membrane proteins. This study describes the mechanism of evolution of the GA733-1 and GA733-2 genes. A full-length cDNA clone for GA733-1 was obtained by screening a human placental library with a genomic DNA probe. Comparative analysis of the cDNA sequence with the previously determined genomic sequence confirmed that GA733-1 is an intronless gene. The GA733-2 gene encoding the monoclonal antibody-defined antigen was molecularly cloned with a cDNA probe and partially sequenced. Comparison of GA733-2 gene sequences with the previously established cDNA sequence revealed that this gene consists of nine exons. The putative promoter regions of the GA733-1 and GA733-2 genes are unrelated. These findings suggest that the GA733-1 gene was formed by the retroposition of the GA733-2 gene via an mRNA intermediate. Prior to retroposition, the GA733-2 gene had been affected by exon shuffling. Analysis of GA733-2 exons revealed that many delineate structural motifs. The GA733-1 retroposon was localized either to chromosome region 1p32-1p31 or to 1p13-1q12, and the GA733-2 founder gene was localized to chromosome 4q.
由单克隆抗体GA733所定义的癌相关抗原的编码基因是一个至少由两种I型膜蛋白组成的家族的成员。本研究描述了GA733 - 1和GA733 - 2基因的进化机制。通过用基因组DNA探针筛选人胎盘文库获得了GA733 - 1的全长cDNA克隆。将该cDNA序列与先前确定的基因组序列进行比较分析，证实GA733 - 1是一个无内含子的基因。用cDNA探针分子克隆了编码单克隆抗体定义抗原的GA733 - 2基因并进行了部分测序。将GA733 - 2基因序列与先前建立的cDNA序列进行比较，发现该基因由9个外显子组成。GA733 - 1和GA733 - 2基因的推定启动子区域不相关。这些发现表明，GA733 - 1基因是通过GA733 - 2基因经mRNA中间体反转录而形成的。在反转录之前，GA733 - 2基因受到外显子重排的影响。对GA733 - 2外显子的分析表明，许多外显子描绘了结构基序。GA733 - 1反转座子定位于染色体区域1p32 - 1p31或1p13 - 1q12，而GA733 - 2原始基因定位于染色体4q。
