The rat casein multigene family. Fine structure and evolution of the beta-casein gene.

The rat casein multigene family. Fine structure and evolution of the beta-casein gene.
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DOI:
10.1016/s0021-9258(18)88885-8
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发表时间:
1985-06
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
W. K. Jones;L. Yu-Lee;S. Clift;T. L. Brown;J. Rosen
W. K. Jones;L. Yu-Lee;S. Clift;T. L. Brown;J. Rosen
中科院分区:
其他
文献类型:
--
作者:
W. K. Jones;L. Yu-Lee;S. Clift;T. L. Brown;J. Rosen

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8个重叠的噬菌体克隆,跨越34.4千碱基对的基因组DNA,包含7.2千碱基对的大鼠β -酪蛋白基因。5‘侧链的前510个碱基对(bp), 3’侧链的110个碱基对,以及所有外显子/内含子连接已测序。β -酪蛋白基因包含9个外显子,大小从21到525bp不等。我们试图通过寻找与乳原激素反应相似的乳蛋白基因之间的序列同源区域,以及寻找先前报道的激素受体结合位点,来确定潜在的调控元件。在5'侧序列保守的前200 bp内,观察到大鼠β -和γ -酪蛋白基因之间有3个同源性大于70%的区域。其中一个含有一个90%与鸡黄体酮受体结合位点同源的区域。保守的5'非编码区、高度保守的信号肽和疏水羧基端区分别由一个单独的外显子编码。相反,进化上保守的β -酪蛋白磷酸化位点是由rna剪接事件形成的。编码β -酪蛋白磷酸化位点的外显子似乎是由基因内复制引起的。基于酪蛋白基因的外显子结构,提出了该基因家族的基因内和基因间外显子复制的进化模型。
Eight overlapping phage clones, spanning 34.4 kilobase pairs of genomic DNA, containing the 7.2-kilobase pair rat beta-casein gene have been isolated and characterized. The first 510 base pairs (bp) of 5' flanking, 110 bp of 3' flanking, and all the exon/intron junctions have been sequenced. The beta-casein gene contains 9 exons ranging in size from 21 to 525 bp. We have attempted to identify potential regulatory elements by searching for regions of sequence homology shared between milk protein genes which respond similarly to lactogenic hormones and by searching for previously reported hormone receptor-binding sites. Within the conserved first 200 bp of 5' flanking sequences 3 regions of greater than 70% homology were observed between the rat beta- and gamma-casein genes. One of these contains a region 90% homologous to the chicken progesterone receptor-binding site. The conserved 5' noncoding region, the highly conserved signal peptide, and the hydrophobic carboxyl-terminal region of the protein are each encoded by a separate exon. In contrast the evolutionarily conserved phosphorylation site of beta-casein is formed by an RNA-splicing event. The exons which encode the phosphorylation sites of beta-casein appear to have resulted from an intragenic duplication. Based upon the exon structure of the casein genes, an evolutionary model of intragenic and intergenic exon duplications for this gene family is proposed.