Comparative analysis of copy number variation in primate genomes

Copy number differences between human and chimpanzee genomic sequences often overlap with regions of intraspecies copy number variation. Copy number variations (CNVs) that occur at orthologous sites in both humans and chimpanzees ('shared' CNVs) are likely to represent unstable genomic regions that have been prone to recurrent rearrangements during primate evolution. Lineage-specific CNVs are also important because they may have been subject to positive selection in specific primate lineages and hence could have contributed both to intra- and interspecies phenotypic diversity. In this study, we reinvestigated the data originally obtained by Perry et al. (2006) relating to chimpanzee CNVs and identified 24 genomic regions with the potential to be chimpanzee-specific CNVs. Since every putative chimpanzee-specific CNV was found in at least two of the 20 chimpanzees originally studied, it would appear as if these 24 CNVs are fairly frequent in chimpanzees. A combination of new mutation, genetic drift, and directional or balancing selection is likely to have influenced the maintenance of these CNVs in the chimpanzee population. Several genes map to the regions encompassed by the chimpanzee-specific CNVs. Some of their human orthologues are already known either to influence the phenotype (e.g., SLC24A4) or to be associated with inherited diseases (e.g., PAK3 and DTNBP1). Although the relatively small number of chimpanzee-specific CNVs (N = 24) among the 355 CNVs originally identified may be in part due to the use of a human BAC array to detect them, we nevertheless surmise that lineage-specific CNVs are not abundant in the chimpanzee. The thorough characterization of CNVs in the great ape genomes is a sine qua non for identifying the human-specific CNVs that may constitute genomic regions which have experienced either positive or negative selection during human evolution.