Alu: Structure, Origin, Evolution, Significance, and Function of One-Tenth of Human DNA

Abstract

Publisher Summary Human repeats have been largely identified and cataloged, accounting for a substantial fraction of the genome. Repetitive sequences are ubiquitously interspersed with single-copy sequences throughout the genome. Interspersed repeats are largely composed of only four distinct families (Alu, LINE 1, MIR, and MaLR), which together comprise 10 to 15% of the entire genome. Alu and LINE 1 subfamilies of different evolutionary ages have different degrees of retrotranspositional activity. This chapter focuses on Alu repeats. Although Alus exemplify many properties of both human and nonhuman repeats, their amplification raises unsolved problems in retroposition. A young Alu subfamily appeared by simple drift of its founder, providing a model for the continual turnover of active repeat-sequence families. Repetitive sequences, ubiquitously distributed throughout the genome, cause various genetic effects. Unequal crossing-over among interspersed repeats duplicates or deletes sequences, thereby, mutating genes. Ubiquitous, homologous repeats, such as Alu, might serve as frequent sites for unequal homologous crossing-over, consequently scrambling their flanking direct repeats.. Unequal Alu–Alu crossing-over duplicates, deletes, or scrambles genetic information. Alu–Alu crossing-over within the low-density lipoprotein receptor gene duplicates exons, thereby, inactivating the gene product, leading to hypercholesterolemia.