Recombination and balanced chromosome polymorphism suggested by DNA sequences 5' to the human delta-globin gene.
Recombination and balanced chromosome polymorphism suggested by DNA sequences 5' to the human delta-globin gene.
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人类 δ 珠蛋白基因 5 端的 DNA 序列表明重组和平衡染色体多态性。
DOI：
10.1073/pnas.80.16.5012
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发表时间：
1983
影响因子：
11.1
通讯作者：
Smithies,O
中科院分区：
文献类型：
--
作者：
Maeda,N;Bliska,JB;Smithies,O
通过从6个人类个体中克隆含有δ-珠蛋白基因5'端双极Alu家族重复序列的3.1-内切酶对EcoRI片段，发现了两种类型的染色体（R和T）。两个T型片段的核苷酸序列完全相同。两个R型片段除一个碱基外完全相同。这两种类型都存在于白人、黑人和东方人中。R和T序列之间的差异（16个碱基替换和2个缺失）主要在片段的5'结构域（在1.7个碱基中差异为0.91%），其中包含双极Alu重复，而片段的3'结构域更保守（在1.4个碱基中差异为0.14%）。为了帮助理解这种人类多态性的历史，克隆了来自黑猩猩的等效片段并测定了其序列。黑猩猩的基因序列与人类的基因序列有39个不同之处，几乎沿着整个3.1-内切酶对片段均匀分布。假设人类和黑猩猩在400万至500万年前分化，数据表明两种类型的人类染色体的分化开始于大约300万年前，但大约40万年前，染色体间重组使两种类型的人类染色体在3'结构域相似。这两条染色体一直保持离散，并在几个种群中持续存在。这些观察结果表明，在人类δ-珠蛋白基因的5'端区域，存在维持平衡的染色体多态性的因素。
Two types of chromosome (R and T) were found by cloning from six human individuals the 3.1-kilobase-pair EcoRI fragment that contains the bipolar Alu family repeat 5' to the delta-globin gene. Two type T fragments were identical in nucleotide sequence. Two type R fragments were identical except for one base. Both types are found in whites, blacks, and orientals. The differences between R and T sequences (16 base substitutions and two deletions) were mostly in the 5' domain of the fragment (0.91% difference in 1.7 kilobases), which contains the bipolar Alu repeat, whereas the 3' domain of the fragment was more conserved (0.14% difference in 1.4 kilobases). To help understand the history of this human polymorphism, the equivalent fragment from a chimpanzee was cloned and its sequence was determined. The chimpanzee sequence differed from both human sequences at 39 positions distributed almost uniformly along the whole 3.1-kilobase-pair fragment. Assuming that humans and chimpanzees diverged 4 to 5 million years ago, the data indicate that the divergence of the two types of human chromosome started about 3 million years ago but about 0.4 million years ago an interchromosomal recombination rendered the two types of human chromosome alike in their 3' domains. The two chromosomes have since remained discrete and have persisted in several populations. These observations suggest that factors are operating to maintain a balanced chromosomal polymorphism in this region 5' to the human delta-globin gene.