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

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.

Divergence patterns of genic copy number variation in natural populations of the house mouse (Mus musculus domesticus) reveal three conserved genes with major population-specific expansions

“…Accordingly, we found that CNVs that overlap with SDs are much more variable between individuals. A large number of CNVs in regions that do not overlap with large SDs are found only in single individuals, concordant with previous findings in humans and apes (Redon et al 2006;Wong et al 2007;Gazave et al 2011). The two categories of CNVs show major functional differences.…”

“…3). Such CNV "hotspots" have been shown to co-occur with SDs, and similar genomic distribution patterns have been reported for great apes and inbred mouse strains (Sharp et al 2005;Perry et al 2006;Egan et al 2007;Graubert et al 2007;Gazave et al 2011). A total of 68% of the CNV genes in our data set overlapped with large SDs in comparison to <8% of the total RefSeq gene set (hypergeometric test; P < 5 × 10 −115 ), indicating strong association between the two.…”

Evolution and diversity of copy number variation in the great ape lineage

“…While there is some evidence that fixed deletions and duplications contribute to morphological differences between humans and great apes (McLean et al 2011;Charrier et al 2012;Dennis et al 2012), a comprehensive assessment of these differences at the level of the genome has not yet been performed. Previous studies of CNV have been predominated by array comparative genomic hybridization (CGH) experiments (Fortna et al 2004;Perry et al 2006;Dumas et al 2007;Gazave et al 2011;Locke et al 2011), which provide limited size resolution, are imprecise in absolute copy number differences, and are biased by probes derived from the human reference genome. Comparisons of reference genomes have been complicated by assessments of a single individual and distinguishing CNVs from assembly errors (The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al 2011;Ventura et al 2011;Prüfer et al 2012).…”

Structural Variants in the Soybean Genome Localize to Clusters of Biotic Stress-Response Genes

“…SV studies have been published in various invertebrate (Dopman and Hartl, 2007;Emerson et al, 2008;Maydan et al, 2010) and mammalian (Graubert et al, 2007;Guryev et al, 2008;Lee et al, 2008;Perry et al, 2008;Gazave et al, 2011;Golzio et al, 2012) systems; however, a high proportion of such studies have been conducted in humans, where there is interest in identifying associations between SV, complex diseases, and neurological disorders Craddock et al, 2010;Sudmant et al, 2010;Girirajan et al, 2011). Domesticated animal species, including dog, cow, and silkworm, have also been the focus of recent investigations of SV (Chen et al, 2009;Nicholas et al, 2009Nicholas et al, , 2011Liu et al, 2010;Sakudoh et al, 2011;Clop et al, 2012).…”