Human-specific duplication and mosaic transcripts: The recent paralogous structure of chromosome 22

In recent decades, comparative chromosomal banding, chromosome painting, an d gene-order studies have shown strong conservation of gross chromosome str ucture and gene order in mammals. However, findings from the human genome s equence suggest an unprecedented degree of recent (<35 million years ago) s egmental duplication. This dynamism of segmental duplications has important implications in disease and evolution. Here we present a chromosome-wide v iew of the structure and evolution of the most highly homologous duplicatio ns (<greater than or equal to>1 kb and greater than or equal to 90%) on chr omosome 22. Overall, 10.8% (3.7/33.8 Mb) of chromosome 22 is duplicated, wi th an average sequence identity of 95.4%. To organize the duplications into tractable units, intron-exon structure and well-defined duplication bounda ries were used to define 78 duplicated modules (minimally shared evolutiona ry segments) with 157 copies on chromosome 22. Analysis of these modules pr ovides evidence for the creation or modification of 11 novel transcripts. C omparative FISH analyses of human, chimpanzee, gorilla, orangutan, and maca que reveal qualitative and quantitative differences in the distribution of these duplications-consistent with their recent origin. Several duplication s appear to be human specific, including a similar to 400-kb duplication (9 9.4%-99.8% sequence identity) that transposed from chromosome 14 to the mos t proximal pericentromeric region of chromosome 22. Experimental and in sil ico data further support a pericentromeric gradient of duplications where t he most recent duplications transpose adjacent to the centromere. Taken tog ether, these data suggest that segmental duplications have been an ongoing process of primate genome evolution, contributing to recent gene innovation and the dynamic transformation of genome architecture within and among clo sely related species.