Copy number variation analysis in the great apes reveals species-specific patterns of structural variation - PubMed (original) (raw)

Comparative Study

. 2011 Oct;21(10):1626-39.

doi: 10.1101/gr.117242.110. Epub 2011 Aug 8.

Fleur Darré, Carlos Morcillo-Suarez, Natalia Petit-Marty, Angel Carreño, Urko M Marigorta, Oliver A Ryder, Antoine Blancher, Mariano Rocchi, Elena Bosch, Carl Baker, Tomàs Marquès-Bonet, Evan E Eichler, Arcadi Navarro

Affiliations

Comparative Study

Copy number variation analysis in the great apes reveals species-specific patterns of structural variation

Elodie Gazave et al. Genome Res. 2011 Oct.

Abstract

Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans.

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Figures

Figure 1.

Figure 1.

Experimental strategy for CNV discovery and validation. The approach is divided into two steps: a first genome-wide discovery phase; and a second targeted validation and refinement phase.

Figure 2.

Figure 2.

CNVR interspecific comparison. For each species, the proportion of its CNVR shared with none, one, two, or three other species is plotted.

Figure 3.

Figure 3.

CNVR clustering tree. Dendrogram showing individuals clustered on the basis of their CNVR similarities. Numbers on the upper lefthand side of each node indicate bootstrap values. Numbers on the righthand side of each node (in italic) are edge numbers. S and B next to the orangutan individuals stand for Sumatra or Borneo, the ancestral geographical origin of the samples. The first letter represents the origin of the sample and the second letter is for the origin of the reference. Individuals are called by short names that are defined in Supplemental Table S1.

Figure 4.

Figure 4.

Frequency distribution of CNVRs in the four species. (A) All species' CNVRs are considered together. (B) Species' CNVRs are split according to their overlap to segmental duplications.

Figure 5.

Figure 5.

Patterns of CNV diversity in the four species. The left axis gives the scale of the πCNV and SCNV values and the right axis scale shows the values of their ratio. In each case, intergenic CNVs are resampled because they are always more numerous than genic CNVs. Values of intergenic πCNV resampled are the mean πCNV obtained in 100,000 random resamplings of N intergenic CNV, N being the number of genic CNV (SCNV genic). We can observe that the resampling procedure maintains the ratio.

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