Recurrent duplication-driven transposition of DNA during hominoid evolution

doi:10.1073/pnas.0605426103

Recurrent duplication-driven transposition of DNA during hominoid evolution

Matthew E. Johnson*,^†,
NISC Comparative Sequencing Program^‡,^§,
Ze Cheng*,
V. Anne Morrison^¶,
Steven Scherer^‖,
Mario Ventura**,
Richard A. Gibbs^‖,
Eric D. Green^††, and
Evan E. Eichler*,^¶,^‡‡

*Department of Genome Sciences and the
^¶Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
^†Department of Genetics and Center for Human Genetics, Case Western Reserve School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106;
^††Genome Technology Branch and
^‡NISC, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;
^‖Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030; and
**Sezione di Genetica, Dipartimento di Anatomia Patologica e di Genetica, University of Bari, 70126 Bari, Italy

Edited by Susan R. Wessler, University of Georgia, Athens, GA, and approved August 18, 2006 (received for review July 1, 2006)

Abstract

The underlying mechanism by which the interspersed pattern of human segmental duplications has evolved is unknown. Based on a comparative analysis of primate genomes, we show that a particular segmental duplication (LCR16a) has been the source locus for the formation of the majority of intrachromosomal duplications blocks on human chromosome 16. We provide evidence that this particular segment has been active independently in each great ape and human lineage at different points during evolution. Euchromatic sequence that flanks sites of LCR16a integration are frequently lineage-specific duplications. This process has mobilized duplication blocks (15–200 kb in size) to new genomic locations in each species. Breakpoint analysis of lineage-specific insertions suggests coordinated deletion of repeat-rich DNA at the target site, in some cases deleting genes in that species. Our data support a model of duplication where the probability that a segment of DNA becomes duplicated is determined by its proximity to core duplicons, such as LCR16a.

Footnotes

^‡‡To whom correspondence should be addressed. E-mail: eee{at}gs.washington.edu
Author contributions: M.E.J. and E.E.E. designed research; M.E.J., N.C.S.P., V.A.M., S.S., M.V., R.A.G., and E.D.G. performed research; M.E.J., Z.C., and E.E.E. analyzed data; and M.E.J. and E.E.E. wrote the paper.
↵ ^§National Institutes of Health Intramural Sequencing Center (NISC) Comparative Sequencing Program: Leadership provided by Robert W. Blakesley, Gerard G. Bouffard, Nancy F. Hansen, Maishali Maskeri, Pamela J. Thomas, and Jennifer C. McDowell.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos: AC092562, AC07264–AC07266, AC097268, AC097270–AC097271, AC097326–AC097328, AC097330–AC097334, AC117273, AC118583, AC119422, AC144359–AC144362, AC144462, AC144590, AC144875–AC144877, AC144879–AC144881, AC145000, AC145025, AC145040, AC145177, AC145239–AC145240, AC145242–AC145243, AC145295, AC145353–AC145354, AC145356, AC145400–AC145403, AC146492, AC146844, AC146898, AC146952, AC147576, AC148534, AC148537– AC148538, AC148619, AC148838–AC148839, AC148841, AC148882, AC149436, AC150449, AC153733, and AC154112).
Abbreviation:

OWM,

Old-World monkey.