| Computational biology complemented by bench science is vital to addressing a wide variety of problems in comparative genomics. Repetitive DNA elements termed Alu have provided a means to address these problems. Alu elements are the most abundant short interspersed elements within the human genome, expanding to about 1 million copies over 65 million years of primate evolution. Alu elements retropose through an RNA intermediate and recently integrated Alu (Ya5, Ya8, Yb8, Yb9, Yc1 and Yc2) have contributed to genetic variation within and between extant primate species and diverse human populations.; We have characterized several hundred young Alu elements and identified 3 new Alu subfamilies (Yc1, Yc2, and Yb9) using the expanding human genome sequence database and polymerase chain reaction based assays. A fourth subfamily (Ya5a2) is believed to harbor a “master” or source gene since members of this family include de novo retroposition events resulting in human diseases. A comparison of sequence mosaics and random genomic dispersal of young Ya5 elements suggests that gene conversion contributes to 10–20% of Alu subfamily nucleotide variation and 2% of all single nucleotide polymorphisms in the human genome. The middle A-region and oligo dA tails of Alus may also serve as nuclei for sequence expansion and the generation of simple sequence repeats.; From 25 to 50% of the recently integrated Alu subfamily members are polymorphic (present or absent) between human genomes. These Alu elements are also absent from non-human primate genomes. Mining Alu elements from the human genome database will facilitate the study of human genetic variation by providing a multitude of diverse “identical-by-descent” genetic markers. |
