Human type I keratin pseudogene φhHaA has functional orthologs in the chimpanzee and gorilla:: evidence for recent inactivation of the human gene after the Pan-Homo divergence
Human type I keratin pseudogene φhHaA has functional orthologs in the chimpanzee and gorilla:: evidence for recent inactivation of the human gene after the Pan-Homo divergence
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DOI：
10.1007/s004390000439
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发表时间：
2001-01-01
期刊：
影响因子：
5.3
通讯作者：
Schweizer, J
中科院分区：
文献类型：
--
作者：
Winter, H;Langbein, L;Schweizer, J
除了9个功能基因外，人I型毛发角蛋白基因簇还包含一个假基因phi hHaA（KRTHAP 1），该假基因被认为已被单个碱基对取代灭活，该取代将过早的TGA终止密码子引入外显子4。对人类、黑猩猩和大猩猩DNA的大规模基因分型显示，不同种族背景的人类中存在纯合的phi hHaA无义突变，但在功能性直系同源黑猩猩（cHaA）和大猩猩（gHaA）基因中不存在。对编码的cHaA和gHaA毛发角蛋白的表达分析突出了当代人类和类人猿的毛发角蛋白表型之间的巨大差异。通过使用gHaA基因作为外群推断，phi hHaA和cHaA基因中同义和非同义取代的相对数目表明人hHaA基因仅在最近失活，即，不到24万年前这意味着在此日期之前以及大约550万年前泛人分歧之后，原始人类的毛发角蛋白表型可能与类人猿的相同。此外，在现存人群中最早的分支谱系中，phi hHaA外显子4无义突变的纯合存在为现代人的“单一非洲起源”假说提供了强有力的支持。
In addition to nine functional genes, the human type I hair keratin gene cluster contains a pseudogene, phi hHaA (KRTHAP1), which is thought to have been inactivated by a single base-pair substitution that introduced a premature TGA termination codon into exon 4. Large-scale genotyping of human, chimpanzee, and gorilla DNAs revealed the homozygous presence of the phi hHaA nonsense mutation in humans of different ethnic backgrounds, but its absence in the functional orthologous chimpanzee (cHaA) and gorilla (gHaA) genes. Expression analyses of the encoded cHaA and gHaA hair keratins served to highlight dramatic differences between the hair keratin phenotypes of contemporary humans and the great apes. The relative numbers of synonymous and non-synonymous substitutions in the phi hHaA and cHaA genes, as inferred by using the gHaA gene as an outgroup, suggest that the human hHaA gene was inactivated only recently, viz., less than 240,000 years ago. This implies that the hair keratin phenotype of hominids prior to this date, and after the Pan-Homo divergence some 5.5 million years ago, could have been identical to that of the great apes. In addition, the homozygous presence of the phi hHaA exon 4 nonsense mutation in some of the earliest branching lineages among extant human populations lends strong support to the "single African origin" hypothesis of modern humans.