Förnzler D, Altschmied J, Nanda I, Kolb R, Baudler M, Schmid M, Schartl M
Physiological Chemistry I, Theodor Boveri Institute for Biosciences (Biocenter), Würzburg, Germany.
Genome Res. 1996 Feb;6(2):102-13. doi: 10.1101/gr.6.2.102.
Hereditary melanoma in Xiphophorus hybrids is caused by the receptor tyrosine kinase Xmrk. Tumor formation is initiated by overexpression of the Xmrk gene, apparently because of insufficient transcriptional control in the melanocytic lineage of hybrid fish. The oncogenic Xmrk resulted from gene duplication and nonhomologous recombination of the corresponding Xmrk proto-oncogene during evolution. By this event Xmrk was translocated downstream of the promoter of another gene, D (for Donor). This raised the question whether both the Xmrk oncogene and D share similar transcriptional control elements. Studies on the genomic organization of D showed that this gene is amplified in the Xiphophorus genome, presumably with all copies clustered on a single chromosome. Surprisingly, at least two completely different, tightly linked genes are included in the amplified segment. We find a ubiquitously expressed zinc finger gene of the krüppel type, followed by a previously unknown gene, which was the partner of the Xmrk proto-oncogene in the recombination generating the Xmrk oncogene. The nucleotide sequence predicts a gene product with very high amino acid similarity to a hypothetical Caenorhabditis elegans protein. The expression pattern is unrelated to that of the Xmrk oncogene suggesting that despite extended sequence homology a new type of promoter was created by this rearrangement.
剑尾鱼杂交种中的遗传性黑色素瘤是由受体酪氨酸激酶Xmrk引起的。肿瘤形成是由Xmrk基因的过表达引发的，这显然是由于杂交鱼黑素细胞谱系中转录控制不足所致。致癌性Xmrk是在进化过程中由相应的Xmrk原癌基因的基因复制和非同源重组产生的。通过这一事件，Xmrk被转移到另一个基因D（供体基因）启动子的下游。这就提出了一个问题，即Xmrk癌基因和D是否共享相似的转录控制元件。对D基因的基因组组织研究表明，该基因在剑尾鱼基因组中被扩增，推测所有拷贝都聚集在一条染色体上。令人惊讶的是，扩增片段中包含至少两个完全不同但紧密相连的基因。我们发现一个普遍表达的克虏伯型锌指基因，其后是一个以前未知的基因，它是在产生Xmrk癌基因的重组中Xmrk原癌基因的伙伴。核苷酸序列预测该基因产物与一种假想的秀丽隐杆线虫蛋白具有非常高的氨基酸相似性。其表达模式与Xmrk癌基因的表达模式无关，这表明尽管序列同源性很高，但这种重排产生了一种新型启动子。
