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. 2006 Nov 21;103(47):17626-31.
doi: 10.1073/pnas.0605426103. Epub 2006 Nov 13.

Recurrent Duplication-Driven Transposition of DNA During Hominoid Evolution

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Free PMC article

Recurrent Duplication-Driven Transposition of DNA During Hominoid Evolution

Matthew E Johnson et al. Proc Natl Acad Sci U S A. .
Free PMC article

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.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
LCR16 organization in human and baboon. The location, copy number, and structure of LCR16 duplications are depicted within the context of an ideogram for human (Left) and Papio hamadryas (PHA) (Right) based on the human genome reference sequence (hg16), BAC-end sequencing, and complete clone insert sequence of baboon clones. With the exception of the ancestral loci, duplication blocks are enumerated based on their position (p–q) on human chromosome 16 (Table 5).
Fig. 2.
Fig. 2.
Sequence alignment between human and nonhuman primate LCR16 loci. (a) Chimpanzee-specific insertion (AC097264) of 81,799 bp between genes DRF1 and FLJ31795 on chromosome 17q21.31. The new insertion consists of three LCR16 duplicons that are shared between human and chimpanzee (LCR16e, w and a) in addition to a flanking 16,820-bp lineage-specific duplication (LCR16a′, Table 9). The 5,962 bp of human sequence corresponding to the preintegration site are deleted in chimpanzee (Table 3). The extent of duplication of the underlying sequence based on WSSD analysis is shown for human (light blue), chimpanzee (pink), and orangutan (dark blue) for this and all subsequent images. (b) Chimpanzee-specific insertion (AC149436) of a segmental duplication mapping to chromosome 16p13.3. The insertion sequence (33,405 bp) consists of LCR16a and a chimpanzee-specific duplication (termed LCR16b′) of 7,403 bp, which is single-copy in human. A corresponding deletion of the integration site (16,100 bp) deletes the serine protease EOS gene in chimpanzee. (c) A 230-kb sequence in orangutan that is completely duplicated (dark blue bar). Two different segments flank the LCR16aw segmental duplication, including a 109-kb segment corresponding to human chromosome 13q34 (chr13:112701583–112831134) and a 99-kb segment from chromosome 16 (chr16:11526252–11625727). Both segments are unique in chimpanzee and human. (d) Orangutan genomic sequence (AC144879) shows the presence of an inserted duplication complex corresponding to human 13q12.11 (chr13:19666603–19839556). A 38,344-bp segment corresponding to the site of insertion in human has been deleted. Several orangutan-specific duplications are noted, including a 21-kb flanking duplication that maps to the corresponding region in human. This property shows that LCR16a and the ancestral locus (LCR16n′) were associated.
Fig. 3.
Fig. 3.
Breakpoint resolution of a chimpanzee insertion. The schematic depicts a segmental duplication insertion of 82 kb and the corresponding deletion of 6.0 kb at the preintegration site with respect to the human reference sequence. PCR breakpoint analysis shows that repeat sequences were present in common ape ancestors but that insertion was specific to chimpanzee and bonobo. Variability in PCR products is due to insertion and deletion of Alu repeats, which are common in repeat-rich regions (22, 42). The preintegration locus consists of 92.7% common repeats.

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