Recent insertion of an Alu element within a polymorphic human-specific Alu insertion.

Alu elements are a family of short interspersed repeats that have mobilized throughout primate genomes by retrotransposition over the past 65 Myr of primate evolution (for a review, see Deininger and Batzer 1993). In the human genome, Alu elements exist in copy numbers of approximately 500,000 per haploid genome, representing approximately 5% of the genome, and they may be classified into groups of related subfamily members that share common diagnostic substitutions (Batzer et al. 1996b). The major subfamily branches (J, S, and Y) seem to have appeared at different evolutionary times, with J being older than S, and S being older than Y. Not only have the Alu elements contributed to the evolution of the primate genomes, but they also contribute up to 0.4% of human genetic disease according to Deininger and Batzer (1999). Two main mechanisms may produce human diseases: direct insertions of Alu elements within genes (0.1% of human genetic disease), and unequal homologous recombination events between Alu repeats (0.3% of human genetic disease). Some of the human Alu elements have retroposed so recently that their insertion at a specific location within the human genome remains polymorphic. These polymorphic insertions have been used as genetic markers in human evolution studies due to their particular properties: they are rapid and easy to type, are apparently selectively neutral, and have known ancestral states. The insertion of an Alu element into the human genome is almost certainly a unique event, making any pair of Alu insertion alleles identical by descent and free of homoplasy. The use of these polymorphisms in a worldwide survey of human populations has confirmed the African origin of modern humans (Batzer et al. 1994; Batzer et al. 1996a; Stoneking et al. 1997). One of these polymorphic Alu insertions is the PV92 Alu site that is located in chromosome 16, and it has been proved to be human-specific (Batzer et al. 1994). The PV92 Alu insertion element belongs to the youngest subfamily of Alu sequences, the Alu Y subfamily, and, within that, to the Ya5 subfamily, which is defined by five diagnostic changes relative to the Y consensus (Batzer et al. 1996b). The PV92 Alu insertion is most frequent in Amerindians (Novick et al. 1998) and East Asians (Stoneking et al. 1997), while it has lower frequencies elsewhere.