Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Hum Genet. 2003 Oct;73(4):823-34. Epub 2003 Sep 22.

An Alu transposition model for the origin and expansion of human segmental duplications.

Author information

  • 1Department of Genetics, Center for Computational Genomics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, 44106, USA.

Abstract

Relative to genomes of other sequenced organisms, the human genome appears particularly enriched for large, highly homologous segmental duplications (> or =90% sequence identity and > or =10 kbp in length). The molecular basis for this enrichment is unknown. We sought to gain insight into the mechanism of origin, by systematically examining sequence features at the junctions of duplications. We analyzed 9,464 junctions within regions of high-quality finished sequence from a genomewide set of 2,366 duplication alignments. We observed a highly significant (P<.0001) enrichment of Alu short interspersed element (SINE) sequences near or within the junction. Twenty-seven percent of all segmental duplications terminated within an Alu repeat. The Alu junction enrichment was most pronounced for interspersed segmental duplications separated by > or =1 Mb of intervening sequence. Alu elements at the junctions showed higher levels of divergence, consistent with Alu-Alu-mediated recombination events. When we classified Alu elements into major subfamilies, younger elements (AluY and AluS) accounted for the enrichment, whereas the oldest primate family (AluJ) showed no enrichment. We propose that the primate-specific burst of Alu retroposition activity (which occurred 35-40 million years ago) sensitized the ancestral human genome for Alu-Alu-mediated recombination events, which, in turn, initiated the expansion of gene-rich segmental duplications and their subsequent role in nonallelic homologous recombination.

PMID:
14505274
[PubMed - indexed for MEDLINE]
PMCID:
PMC1180605
Free PMC Article

Images from this publication.See all images (9)Free text

Figure  1
Figure  2
Figure  3
Figure  4
Figure  5
Figure  6
Figure  A
Figure  B
Figure  C
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk