Recent amplification of the human FRG1 gene during primate evolution

There is evidence of multiple copies of the FSHD Region Candidate Gene 1 (FRG1) in humans. Analysis of human FRG1 ESTs showed many of them to be non-processed pseudogenes dispersed throughout the genome. To determine when the amplification of FRG1 occurred, we used a PCR-based approach to identify FRG1 sequences from great apes, chimpanzee, gorilla and orang-utan, and an Old World monkey, Macaca mulatta. In common with humans, multiple copies of FRG1 were detected in the great apes. However, in Macaca mulatta, only two FRG1 loci were identified, one presumed to be the homologue of the human chromosome 4q gene. This is strikingly similar to the distribution of a dispersed 3.3-kb repeat family in primates. A member of this family, D4Z4, maps to the subtelomeric region of 4q, in close proximity to FRG1. We propose that an ancestral duplication of distal 4q included FRG1. This duplication is present in Macaca mulatta whose divergence from hominoids is thought to have occurred at least 33 million years ago. We propose that this telomeric region then underwent further amplification and dispersion events in the great ape lineage, with copies of FRG1 and the 3.3-kb repeats being localized in heterochromatic regions.