AFRICAN ORIGIN OF HUMAN-SPECIFIC POLYMORPHIC ALU INSERTIONS

Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few ''master'' gene s. Among the 500,000 Alu elements in the human genome are members of t he human-specific subfamily that are not feued in the human species; t hat 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 p oint to determine genotypes based on the presence or absence of the Al u element. These four polymorphic Alu insertions were shown to be abse nt 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 differenti ation among groups. No significant associations were found among the f our loci, consistent with their location on different chromosomes. A m aximum-likelihood tree of population relationships showed four major g roupings consisting of Africa, Europe, Asia/Americas, and Australia/Ne w Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is tha t the ancestral state is known to be the absence of the Alu element, a nd the presence of the Alu element at a particular chromosomal site re flects a single, unique event in human evolution. A hypothetical ances tral group can then be included in the tree analysis, with the frequen cy 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 con cordant with other diverse data sets, which lends further support to t he recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution.