Batzer and Deininger 2002 Nature Reviews Genetics

Batzer and deininger 2002 nature reviews genetics

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Unformatted text preview: REVIEWS ALU REPEATS AND HUMAN GENOMIC DIVERSITY Mark A. Batzer* and Prescott L. Deininger‡§ During the past 65 million years, Alu elements have propagated to more than one million copies in primate genomes, which has resulted in the generation of a series of Alu subfamilies of different ages. Alu elements affect the genome in several ways, causing insertion mutations, recombination between elements, gene conversion and alterations in gene expression. Alu-insertion polymorphisms are a boon for the study of human population genetics and primate comparative genomics because they are neutral genetic markers of identical descent with known ancestral states. The role of mobile elements in the shaping of eukaryotic genomes is becoming more and more recognized. Mobile elements make up over 45% of the human genome. These elements continue to amplify and, as a result of negative effects of their transposition, they contribute to a notable number of human diseases. All eukaryotic genomes contain mobile elements, although the proportion and activity of the classes of elements varies widely between genomes. Mobile elements are important in insertional mutagenesis and unequal homologous recombination events. They use extensive cellular resources in their replication, expression and amplification. There is considerable debate as to whether they are primarily an intracellular plague that attacks the host genome and exploits cellular resources, or whether they are tolerated because of their occasional positive influences in genome evolution. The recent completion of the draft sequence of the human genome provides an unprecedented opportunity to assess the biological properties of Alu repeats and the influence that they have had on the architechture of the human genome. Here, we present an overview of the biology and the impact of Alu repeats — the largest family of mobile elements in the human genome. Discovery and origin of Alu elements MICROSATELLITE A class of repetitive DNA that is made up of repeats that are 2–8 nucleotides in length. They can be highly polymorphic and are frequently used as molecular markers in population genetics studies. *Department of Biological Sciences, Biological Computation and Visualization Center, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA. ‡Tulane Cancer Center, SL-66, Department of Environmental Health Sciences, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA. §Laboratory of Molecular Genetics, Alton Ochsner Medical Foundation, 1516 Jefferson Highway, New Orleans, Louisiana 70121, USA. Correspondence to M.A.B. e-mail: DOI: 10.1038/nrg798 The term ‘repetitive element’ describes various DNA sequences that are present in multiple copies in the genomes in which they reside. Repetitive elements can be subdivided into those that are tandemly arrayed (for example, MICROSATELLITES, MINISATELLITES and telomeres) or interspersed (for example, mobile elements and processed PSEUDOGENES). Interspersed elements can be subdivided on the basis of size, with short interspersed elements (SINEs) being less than 500 bp long1–4. Alu SINEs were identified originally almost 30 years ago as a component in human DNA 5,6 RENATURATION CURVES . The name ‘Alu elements’ was given to these repeated sequences as members of this family of repeats contain a recognition site for the restriction enzyme AluI (REF. 5). Subsequent detailed analyses of this portion of the renaturation curves led to sequence analysis of individual Alu elements. They were initially cloned using linkers with BamHI restriction endonuclease sites that resulted in the generation of Bam-linked ubiquitous repeat (BLUR) clones7,8. Full-length Alu elements are ~300 bp long and are commonly found in introns, 3′ untranslated regions of genes and intergenic genomic regions (BOX 1). Initial estimates indicated that these mobile elements were present in the human genome at an extremely high copy number (~500,000 copies) 7. Recently, a detailed analysis of the draft sequence of the human genome has shown that, out of more than one million copies, Alu elements are the most abundant SINEs, which makes them the most abundant of all mobile elements in the human genome9. Because of 370 | MAY 2002 | VOLUME 3 © 2002 Nature Publishing Group REVIEWS their high copy number, the Alu gene family comprises more than 10% of the mass of the human genome9 and as Alu sequences accumulate preferentially in gene-rich regions, they are not uniformly distributed in the human genome9–11. The origin and amplification of Alu elements are evolutionarily recent events that coincided with the radiation of primates in the past 65 million years12. Detailed sequence analysis of the structure of Alu element RNAs has indicated that Alu elements were ancestrally derived from the 7SL RNA gene, which forms part of the ribosome complex13. Therefore,...
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