Winter H, Langbein L, Krawczak M, Cooper D N, Jave-Suarez L F, Rogers M A, Praetzel S, Heidt P J, Schweizer J
German Cancer Research Center, Heidelberg, Germany.
Hum Genet. 2001 Jan;108(1):37-42. doi: 10.1007/s004390000439.
In addition to nine functional genes, the human type I hair keratin gene cluster contains a pseudogene, phihHaA (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 phihHaA 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 phihHaA 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 phihHaA 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.
除了九个功能基因外，人类I型毛发角蛋白基因簇还包含一个假基因phihHaA（KRTHAP1），它被认为是由于一个单碱基对替换而失活，该替换在第4外显子中引入了一个过早的TGA终止密码子。对人类、黑猩猩和大猩猩DNA进行的大规模基因分型显示，不同种族背景的人类中均存在phihHaA无义突变的纯合子，但在功能上与之对应的黑猩猩（cHaA）和大猩猩（gHaA）基因中则不存在。对编码的cHaA和gHaA毛发角蛋白的表达分析突出了当代人类与大猩猩毛发角蛋白表型之间的显著差异。以gHaA基因为外类群推断，phihHaA和cHaA基因中同义替换和非同义替换的相对数量表明，人类hHaA基因是最近才失活的，即不到24万年前。这意味着在此日期之前以及约550万年前泛人类分化之后的原始人类毛发角蛋白表型可能与大猩猩的相同。此外，现存人类群体中一些最早期分支谱系中phihHaA第4外显子无义突变的纯合子存在，为现代人类的“单一起源于非洲”假说提供了有力支持。
