Genomic structure of the orthologous region to human 7q11.23 in the different primates, and hypothetical model for the sequential evolution of the region. (A) Schematic representation of the chromosome region in each primate species. A first inversion of the WBS region must have occurred in an ancestral chromosome to all hominoids. The orangutan and gorilla chromosomes appear identical except for the absence of the block C-block A junction in orangutan, whereas gorilla and chimpanzee chromosomes are identical except for the segmental duplication containing the HIP1 gene in chimpanzee. (B) Predicted human lineage-specific rearrangements from a hypothetical ancestral chromosome identical to that of gorilla. A unique complex intrachromosomal rearrangement from the ancestral chromosome created an intermediate chromosomal structure by two shuffling events between Alu elements, represented as 1 and 2 indicating the order of occurrence. By a similar mechanism of Alu-mediated duplicative transposition, the chimpanzee chromosome could have been generated (data not shown), with a duplication of the HIP1 containing block instead. A putative intrachromosomal paracentric inversion in the intermediate chromosome could have been mediated by the blocks C, which are flanking the region in inverted orientation. Interchromosomal NAHR in an inversion carrier of this intermediate chromosome could have led to duplication of the entire segmental duplication-containing blocks C, A, and B onto the centromeric position. The presence of Alu elements located at the edges of the blocks suggests Alu-mediated genome shuffling in these final steps of the generation of large segmental duplications.
