Plasticity of human chromosome 3 during primate evolution

Abstract

Comparative FISH mapping of some 150 YAC and BAC clones from human chromosome 3 in orangutans (PPY), siamang gibbon (HSY), silvered-leaf monkey (PCR) and Geoffroys marmoset (CGE) revealed that hominoid chromosome evolution is more complex than suggested by classical chromosome banding and painting. The large-scale inversions, fissions and translocations in the five primate species studied involve at least 14 different evolutionary breakpoints. Many evolutionary rearrangements, i.e. the pericentric inversions leading to PPY 2, were not simple breakage and reunion events. The breakpoint regions that distinguish HSA 3p25.1, 3p12.3 and 3q21 from PPY 2 contain paralogous sequence blocks, which were prone to microduplications and microdeletions during evolution of the hominoid genome. A 6.5 Mb interval syntenic to HSA 3q21 contains four independent evolutionary breakpoints, namely at 130-132 Mb in PPY, 130-133.8 Mb in HSY, 127.3-132 Mb in PCR and 130-132 Mb in CGE. By FISH, three breakpoints in orangutan, gibbon and Old World monkey were localized in a 320 kb contig of BACs RP11-93K22, RP11-77P16 and RP11-687B8. 35 PCR primer pairs which amplify specific DNA fragments along the entire length of this contig were tested on flow sorted PPY and HSY chromosomes and the respective breakpoints were narrowed further to a 230 kb interval in RP11-93K22 and RP11-77P16. About 200 kb of this contig were deleted from the HSA 3q21-syntenic inversion breakpoint in PPY 2 and the translocation breakpoint leading to HSY 10 and 21. The deleted segment represents part of an ancestral duplication of HSA 3q21-paralogous sequences in human, orangutan and gibbon genomes. Collectively, our results suggest that particular regions in the hominoid genome are more susceptible to evolutionary chromosome reshuffling. Large-scale chromosome rearrangements, microduplications and microdeletions can be considered as different aspects of an inherent instability of these regions. Genome architecture involving low-copy repeats has played an important role during primate speciation.