A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications - PubMed (original) (raw)

Comparative Study

A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications

Xinwei She et al. Genome Res. 2006 May.

Abstract

Compared with other sequenced animal genomes, human segmental duplications appear larger, more interspersed, and disproportionately represented as high-sequence identity alignments. Global sequence divergence estimates of human duplications have suggested an expansion relatively recently during hominoid evolution. Based on primate comparative sequence analysis of 37 unique duplication-transition regions, we establish a molecular clock for their divergence that shows a significant increase in their effective substitution rate when compared with unique genomic sequence. Fluorescent in situ hybridization (FISH) analyses from 1053 random nonhuman primate BACs indicate that great-ape species have been enriched for interspersed segmental duplications compared with representative Old World and New World monkeys. These findings support computational analyses that show a 12-fold excess of recent (>98%) intrachromosomal duplications when compared with duplications between nonhomologous chromosomes. These architectural shifts in genomic structure and elevated substitution rates have important implications for the emergence of new genes, gene-expression differences, and structural variation among humans and great apes.

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Figures

Figure 1.

Figure 1.

Distribution of recent segmental duplications in the human genome. (A) Sequence identity. Interchromosomal (red) and intrachromomal (blue) segmental duplications in the human genome sequence (May 2004 build) were binned according to their divergence, and the total number of aligned basepairs was determined. Divergence (K) is calculated as the number of substitutions per site between the two duplication alignments. (B) Chromosomal distribution. The distribution of recent segmental duplications is depicted with the color bars representing different percent identities. The distribution within each chromosome was calculated as the proportion of pairwise alignments at each percent identity.

Figure 2.

Figure 2.

Single nucleotide substitution in unique and duplicated genomic regions. (A) Divergence of unique genomic regions. A scatter plot of genetic distances (changes/basepair, Kimura two-parameter model) determined from nonoverlapping 3-kb sliding windows for human–chimpanzee (5.0 Mb), human–baboon (5.0 Mb), human–marmoset (4.0 Mb), and human–lemur (2.8 Mb) sequence alignments. A total of 56 marmoset windows and 182 lemur windows were >0.50 in Kimura distance and thus not shown. The mean ± standard deviation (from the number of windows) are shown for each comparison based on the number of windows assessed (see Supplemental Table S1a for more details). (B) Divergence of duplicated genomic regions. Genomic sequence alignments that contain segmental duplications and that transition into unique sequence were examined for divergence between humans and nonhuman primates (baboon and chimpanzee). Duplicated and unique portions were considered separately in this analysis and compared with unique regions in A. Duplicated regions show an increase in substitution irrespective of their duplication or unique status based on alignment to the human genome.

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