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大猩猩甲胎蛋白基因的结构与灵长类动物的分化

Structure of the gorilla alpha-fetoprotein gene and the divergence of primates.

作者信息

Ryan S C, Zielinski R, Dugaiczyk A

机构信息

Department of Biochemistry, University of California, Riverside 92521.

出版信息

Genomics. 1991 Jan;9(1):60-72. doi: 10.1016/0888-7543(91)90221-y.

DOI:10.1016/0888-7543(91)90221-y
PMID:1706310
Abstract

The sequence of the gorilla alpha-fetoprotein gene, including 869 base pairs of the 5' flanking region and 4892 base pairs of the 3' flanking region (24,607 in total), was determined from two overlapping lambda phage clones. The sequence extends 18,846 base pairs from the Cap site to the polyadenylation site, and it reveals that the gene is composed of 15 exons, which are symmetrically placed within three domains of alpha-fetoprotein. The deduced polypeptide chain is composed of a 19-amino-acid leader peptide, followed by 590 amino acids of the mature protein. The RNA polymerase II binding site, TATAAAA, and the promoter element, CCAAC, are positioned at -21 and -65 from the Cap site, respectively. The polyadenylation signal, AATAAA, is located in the last exon, which is untranslated. The sequence for the gorilla alpha-fetoprotein gene was compared with that of the previously published human alpha-fetoprotein gene (P. E. M. Gibbs, R. Zielinski, C. Boyd, and A. Dugaiczyk, 1987, Biochemistry 26: 1332-1343). Four types of repetitive sequence elements were found in identical positions in both species. However, one Alu and one Xba DNA repeat within introns 4 and 7, respectively, of the human gene are absent from orthologous positions in the gorilla. The Alu and the Xba DNA repeats probably emerged in the human genome after the human/gorilla divergence and became established novelties in the human lineage. There are 363/21,523 mutational changes between human and gorilla, amounting to 1.69% DNA divergence between the two primate species. The value of 1.69% is lower than the 2.27% obtained from melting temperatures of hybrids between human and gorilla genomic DNA (C. G. Sibley and J. E. Ahlquist, 1984, J. Mol. Evol. 26: 99-121). At the protein level, Homo sapiens differs from Gorilla gorilla only at 4 of 609 amino acid positions (0.66%) in the alpha-fetoprotein sequence. This difference signifies a lower rate of molecular divergence for the alpha-fetoprotein gene in primates, as compared to rodents.

摘要

从两个重叠的λ噬菌体克隆中确定了大猩猩甲胎蛋白基因的序列,包括5'侧翼区的869个碱基对和3'侧翼区的4892个碱基对(总共24,607个碱基对)。该序列从帽位点延伸至聚腺苷酸化位点达18,846个碱基对,并且揭示该基因由15个外显子组成,这些外显子对称地分布在甲胎蛋白的三个结构域内。推导的多肽链由一个19个氨基酸的前导肽组成,其后是590个氨基酸的成熟蛋白。RNA聚合酶II结合位点TATAAAA和启动子元件CCAAC分别位于距帽位点-21和-65处。聚腺苷酸化信号AATAAA位于最后一个未翻译的外显子中。将大猩猩甲胎蛋白基因的序列与先前发表的人类甲胎蛋白基因的序列(P.E.M. Gibbs、R. Zielinski、C. Boyd和A. Dugaiczyk,1987年,《生物化学》26卷:1332 - 1343页)进行了比较。在两个物种的相同位置发现了四种重复序列元件类型。然而,人类基因第4和第7内含子中的一个Alu和一个Xba DNA重复序列在大猩猩的直系同源位置不存在。Alu和Xba DNA重复序列可能在人类/大猩猩分化后出现在人类基因组中,并在人类谱系中成为新确立的序列。人类和大猩猩之间有363/21,523个突变变化,这两个灵长类物种之间的DNA差异为1.69%。1.69%的值低于从人类和大猩猩基因组DNA杂交体的解链温度获得的2.27%(C.G. Sibley和J.E. Ahlquist,1984年,《分子进化杂志》26卷:99 - 121页)。在蛋白质水平上,智人与大猩猩在甲胎蛋白序列的609个氨基酸位置中仅有4个位置不同(0.66%)。与啮齿动物相比,这种差异表明灵长类中甲胎蛋白基因的分子分化率较低。

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