Batzer M A, Stoneking M, Alegria-Hartman M, Bazan H, Kass D H, Shaikh T H, Novick G E, Ioannou P A, Scheer W D, Herrera R J
Human Genome Center, Lawrence Livermore National Laboratory, CA 94551.
Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12288-92. doi: 10.1073/pnas.91.25.12288.
Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution.
Alu元件是一类散布重复序列，通过少数“主”基因的逆转座作用在灵长类基因组中移动。人类基因组中50万个Alu元件里，有属于人类特有的亚家族成员，这些成员在人类物种中并非固定存在；也就是说，并非所有染色体在特定基因座上都携带Alu元件。通过一种基于PCR的快速检测方法分析了四个这样的多态性人类特有的Alu插入，该方法使用位于插入点两侧的引物，根据Alu元件的有无来确定基因型。结果显示，许多非人类灵长类动物的基因组中不存在这四个多态性Alu插入，这与它们在人类/非洲猿分化后的某个时候作为人类遗传多态性出现的情况一致。对来自世界各地16个种群的664名无关个体的分析表明，种群内部存在大量变异，且种群间存在显著的遗传分化。在这四个基因座之间未发现显著关联，这与它们位于不同染色体上的情况一致。种群关系的最大似然树显示有四个主要分组，分别由非洲、欧洲、亚洲/美洲和澳大利亚/新几内亚组成，这与基于其他基因座的类似树状图一致。多态性Alu插入的一个特别有用的特征是，已知其祖先状态是不存在Alu元件，而在特定染色体位点上Alu元件的存在反映了人类进化中的一个单一、独特事件。然后可以将一个假设的祖先群体纳入树状图分析，将每个插入的频率设为零。与最大似然树相连的祖先群体位于非洲分支内，这表明这些多态性Alu插入起源于非洲。这些数据与其他各种数据集一致，进一步支持了现代人类起源于非洲的假说。多态性Alu插入代表了一种用于研究人类种群结构和进化的遗传变异来源。
