Evolution of the apolipoproteins. Structure of the rat apo-A-IV gene and its relationship to the human genes for apo-A-I, C-III, and E.
Evolution of the apolipoproteins. Structure of the rat apo-A-IV gene and its relationship to the human genes for apo-A-I, C-III, and E.
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发表时间：
1986-05
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通讯作者：
M. Boguski;E. Birkenmeier;N. Elshourbagy;J. Taylor;J. Gordon
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作者：
M. Boguski;E. Birkenmeier;N. Elshourbagy;J. Taylor;J. Gordon
我们测定了大鼠载脂蛋白(apo-)A-IV基因的核苷酸序列，并分析了其与人类载脂蛋白A-I、E和C-III基因的结构和进化关系。大鼠A-IV基因全长2.4kb，由三个外显子(142、126和1157个碱基对)组成，中间有两个内含子(277和673个碱基对)。5‘-非翻译区和大部分信号肽由第一外显子编码。因此，与所有其他已知的载脂蛋白基因相比，apo-A-IV基因在其mRNA的5‘-非翻译区缺乏内含子。编码两亲性多肽的序列跨越大鼠A-IV基因的第二和第三外显子。我们证明了人类载脂蛋白基因也是如此。这个基因家族似乎是通过复制祖先的微型基因而进化出来的，这导致了两个外显子的形成。此后，这些序列的进化被编码两亲性多肽的重复单位的外显子内扩增所主导。这些重复序列的序列差异导致了载脂蛋白的功能分化。然而，基本的两亲性模式的保守使得这个蛋白质家族的成员能够保留他们的脂结合特性。
We have determined the nucleotide sequence of the rat apolipoprotein (apo-) A-IV gene and analyzed its structural and evolutionary relationships to the human apolipoprotein A-I, E, and C-III genes. The rat A-IV gene is 2.4 kilobases in size and consists of three exons (142, 126, and 1157 base pairs) interrupted by two introns (277 and 673 base pairs). The 5'-nontranslated region and most of the signal peptide are encoded by the first exon. Thus, the apo-A-IV gene lacks an intron in the 5'-nontranslated region of its mRNA in contrast to all other known apolipoprotein genes. Sequences coding for amphipathic docosapeptides span both the second and third exons of the rat A-IV gene. We demonstrate that this is also true for the human apolipoprotein genes. This gene family seems to have evolved by the duplication of an ancestral minigene that resulted in the formation of two exons. Thereafter, evolution of these sequences was dominated by intraexonic amplification of repeating units coding for amphipathic peptides. Sequence divergence of these repeats resulted in the functional differentiation of the apolipoproteins. However, conservation of the fundamental amphipathic pattern allowed members of this protein family to retain their lipid-binding properties.