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Vol. 12, Issue 10, 1483-1495, October 2002

LETTER
Retroelement Distributions in the Human Genome: Variations Associated With Age and Proximity to Genes

Patrik Medstrand,1,4 Louie N. van de Lagemaat,2,3,4 and Dixie L. Mager2,3,5

1 Department of Cell and Molecular Biology, Section for Developmental Biology, Lund University, 22184, Lund, Sweden; 2 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z1L3, Canada; 3 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T1Z1 Canada

Remnants of more than 3 million transposable elements, primarily retroelements, comprise nearly half of the human genome and have generated much speculation concerning their evolutionary significance. We have exploited the draft human genome sequence to examine the distributions of retroelements on a genome-wide scale. Here we show that genomic densities of 10 major classes of human retroelements are distributed differently with respect to surrounding GC content and also show that the oldest elements are preferentially found in regions of lower GC compared with their younger relatives. In addition, we determined whether retroelement densities with respect to genes could be accurately predicted based on surrounding GC content or if genes exert independent effects on the density distributions. This analysis revealed that all classes of long terminal repeat (LTR) retroelements and L1 elements, particularly those in the same orientation as the nearest gene, are significantly underrepresented within genes and older LTR elements are also underrepresented in regions within 5 kb of genes. Thus, LTR elements have been excluded from gene regions, likely because of their potential to affect gene transcription. In contrast, the density of Alu sequences in the proximity of genes is significantly greater than that predicted based on the surrounding GC content. Furthermore, we show that the previously described density shift of Alu repeats with age to domains of higher GC was markedly delayed on the Y chromosome, suggesting that recombination between chromosome pairs greatly facilitates genomic redistributions of retroelements. These findings suggest that retroelements can be removed from the genome, possibly through recombination resulting in re-creation of insert-free alleles. Such a process may provide an explanation for the shifting distributions of retroelements with time.

4 These authors contributed equally to this work.

5 Corresponding author.

12:1483-1495 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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