Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009;74:355-62.
doi: 10.1101/sqb.2009.74.011. Epub 2009 Aug 28.

The Evolution of Human Segmental Duplications and the Core Duplicon Hypothesis

Affiliations
Free PMC article
Review

The Evolution of Human Segmental Duplications and the Core Duplicon Hypothesis

T Marques-Bonet et al. Cold Spring Harb Symp Quant Biol. .
Free PMC article

Abstract

Duplicated sequences are important sources of genetic instability and in the evolution of new gene function within species. Hominids have a preponderance of intrachromosomal duplications organized in an interspersed fashion, as opposed to tandem duplications, which are common in other mammalian genomes such as mouse, dog, and cow. Multiple lines of evidence, including sequence divergence, comparative primate genomes, and fluorescence in situ hybridization (FISH) analyses, point to an excess of segmental duplications in the common ancestor of humans and African great apes. We find that much of the interspersed human duplication architecture within chromosomes is focused around common sequence elements referred to as "core duplicons." These cores correspond to the expansion of gene families, some of which show signatures of positive selection and lack orthologs present in other mammalian species. This genomic architecture predisposes apes and humans not only to extensive genetic diversity, but also to large-scale structural diversity mediated by nonallelic homologous recombination. In humans, many de novo large-scale genomic changes mediated by these duplications are associated with neuropsychiatric and neurodevelopmental disease. We propose that the disadvantage of a high rate of new mutations is offset by the selective advantage of newly minted genes within the cores.

Figures

Figure 1
Figure 1
Percentage of identity distribution of mouse versus human SDs. Note the increase of interchromosomal duplications and the higher proportion of recent SDs in humans and the excess of intrachromosomal (tandem) duplications in mouse.
Figure 2
Figure 2
(A) Venn diagram showing shared and lineage-specific duplications among four primate genomes. Estimates were based on identifying regions of excess read-depth to the human assembly genome. Numbers underlined are copy-number corrected to avoid the bias of nonhuman-specific SDs. (B) Assignment of duplications and rate estimation of Mbp/Myr for each branch. Note the excess of duplication rate in the branch leading to the common ancestor of human and chimpanzee (Marques-Bonet et al. 2009).
Figure 3
Figure 3
Hierarchical clustering of human duplication blocks based on ancestral duplicon content. The termini of each branch represent one of 437 duplication blocks, which cluster into 24 distinct groups, 14 of which are restricted to a specific chromosome and 10 of which are mixed (M) among chromosomes mapping largely to subtelomeric (S) or pericentromeric (P) regions of the genome. An expanded view of chromosome 16 is shown (Fig. 5) (Jiang et al. 2007).
Figure 4
Figure 4
Comparative schematic showing the distribution of LCR16 duplications. Color bars shows LCR16 duplicons. In human, the LCR16a core duplicon (red) is present within most duplication blocks on chromosome 16; all corresponding duplications are single copy in baboon, but in orangutan, LCR16a exists at nonorthologous locations and on different chromosomes (chromosome 13) in association with a new suite of orangutan-specific duplications at the periphery. Map locations are numbered according to the human reference with ancestral locations flagged by an asterisk.
Figure 5
Figure 5
SDs and disease. Detailed duplicon composition of duplication blocks are shown along an ideogram of human chromosome 16. Duplications mediating recurrent deletions and duplications associated with disease are indicated (Ballif et al. 2007; Jiang et al. 2007; Ullmann et al. 2007; Kumar et al. 2008; Weiss et al. 2008; Hannes et al. 2009).

Similar articles

See all similar articles

Cited by 20 articles

See all "Cited by" articles

LinkOut - more resources

Feedback