McEvoy S M, Maeda N
Department of Genetics, University of Wisconsin, Madison 53706.
J Biol Chem. 1988 Oct 25;263(30):15740-7.
Southern blot analyses of genomic DNA show that new world monkeys have only one haptoglobin gene but that chimpanzees, gorillas, orangutans, and old world monkeys have three. Humans have two: haptoglobin (Hp) and haptoglobin-related (Hpr). These observations suggest that a triplication of the haptoglobin locus occurred after the divergence of the new world monkeys, followed by a deletion of one locus in humans. To investigate these events, we have cloned the haptoglobin gene cluster in chimpanzee. The organization of the Hp and Hpr genes in chimpanzees is the same as in humans, including a retrovirus-like sequence in the first intron of Hpr. The third gene, which we name Hpp for haptoglobin primate, is 16 kilobases downstream of Hpr. A second copy of the retrovirus-like sequence occurs between Hpr and Hpp. The nucleotide sequence of the chimpanzee Hpp gene suggests that it may code for a functional protein, but the chimpanzee Hpr gene has a single base deletion in exon 5 that causes a frameshift. Comparison of the human and chimpanzee sequences suggests that the human Hpr gene was generated by a homologous unequal crossover between ancestral Hpr and Hpp genes. The crossover point lies within a 1.3-kilobase region containing exon 5 and 500 nucleotides 3' to the genes, but the exact point is obscured by a subsequent gene conversion event.
对基因组DNA的Southern印迹分析表明，新大陆猴只有一个触珠蛋白基因，而黑猩猩、大猩猩、猩猩和旧大陆猴有三个。人类有两个：触珠蛋白（Hp）和触珠蛋白相关蛋白（Hpr）。这些观察结果表明，触珠蛋白基因座在新大陆猴分化后发生了三倍化，随后人类中一个基因座发生了缺失。为了研究这些事件，我们克隆了黑猩猩的触珠蛋白基因簇。黑猩猩中Hp和Hpr基因的组织方式与人类相同，包括Hpr第一个内含子中的一个类似逆转录病毒的序列。第三个基因，我们将其命名为灵长类触珠蛋白（Hpp），位于Hpr下游16千碱基处。在Hpr和Hpp之间出现了第二个类似逆转录病毒的序列拷贝。黑猩猩Hpp基因的核苷酸序列表明它可能编码一种功能性蛋白质，但黑猩猩Hpr基因在第5外显子中有一个单碱基缺失，导致移码。人类和黑猩猩序列的比较表明，人类Hpr基因是由祖先Hpr和Hpp基因之间的同源不等交换产生的。交换点位于一个1.3千碱基的区域内，该区域包含第5外显子和基因3'端的500个核苷酸，但确切位置被随后的基因转换事件所掩盖。
