Jansen H W, Bister K
Virology. 1985 Jun;143(2):359-67. doi: 10.1016/0042-6822(85)90376-9.
The nucleotide sequence of the chicken gene c-mil was determined within and around all regions homologous to the oncogene v-mil of avian retrovirus MH2. The regions of homology to the previously determined v-mil sequence, ranging in size from 28 to 177 base pairs (bp), are distributed over 14 kilobase pairs (kbp) of the chicken genome and are organized in 11 exons. All exon-intron boundaries of c-mil, except the 5' boundary of exon 1 and the 3' boundary of exon 11, were unambiguously defined by the identification of consensus splice donor and acceptor sites precisely at positions where homology to v-mil ceases or resumes. The homology to v-mil starts within the coding sequence of exon 1 and ends within the 3' untranslated region of exon 11, 12 nucleotides downstream from the nonsense codon terminating the large open reading frame shared between c-mil and v-mil. The c-mil and v-mil sequences differ at only 7 out of 1153 nucleotide positions, and the predicted sequences of v-mil and c-mil proteins differ by one conservative and four nonconservative substitutions among 379 amino acid residues. Hence, the carboxy-terminal domains of the MH2 gag-mil hybrid protein and of the putative c-mil protein are very similar. However, the amino-terminal domain of the cellular protein is possibly encoded by additional 5' c-mil sequences not present in the transduced v-mil oncogene, while that of the MH2 hybrid protein is encoded by viral gag sequences. The sequence analysis also revealed that c-mil and c-myc derived sequences are immediately adjacent on the MH2 genome carrying both the v-mil and the v-myc oncogene. Hence, transduction of c-mil into MH2 involved recombination, at the 3' site, with either the c-myc locus or a previously transduced v-myc gene, and, at the 5' site, with gag sequences of the transducing virus. At both sites, no significant homologies were found between the sequence elements involved in the recombination.
测定了鸡基因c-mil与禽逆转录病毒MH2的致癌基因v-mil同源的所有区域及其周围的核苷酸序列。与先前确定的v-mil序列的同源区域大小从28到177个碱基对（bp）不等，分布在鸡基因组的14千碱基对（kbp）上，并由11个外显子组成。c-mil的所有外显子-内含子边界，除了外显子1的5'边界和外显子11的3'边界外，通过在与v-mil的同源性终止或恢复的精确位置鉴定共有剪接供体和受体位点而明确界定。与v-mil的同源性在外显子1的编码序列内开始，并在外显子11的3'非翻译区内结束，位于终止c-mil和v-mil之间共享的大开放阅读框的无义密码子下游12个核苷酸处。c-mil和v-mil序列在1153个核苷酸位置中仅7个位置不同，v-mil和c-mil蛋白的预测序列在379个氨基酸残基中有1个保守取代和4个非保守取代。因此，MH2 gag-mil杂交蛋白和推定的c-mil蛋白的羧基末端结构域非常相似。然而，细胞蛋白的氨基末端结构域可能由转导的v-mil致癌基因中不存在的额外5' c-mil序列编码，而MH2杂交蛋白的氨基末端结构域由病毒gag序列编码。序列分析还显示，携带v-mil和v-myc致癌基因的MH2基因组上，c-mil和c-myc衍生序列紧邻。因此，将c-mil转导到MH2中涉及在3'位点与c-myc基因座或先前转导的v-myc基因发生重组，以及在5'位点与转导病毒的gag序列发生重组。在这两个位点，重组所涉及的序列元件之间未发现明显同源性。
