Recent amplification of the human FRG1 gene during primate evolution

There is evidence of multiple copies of the FSHD Region Candidate Gene 1 (F RG1) in humans. Analysis of human FRG1 ESTs showed many of them to be non-p rocessed pseudogenes dispersed throughout the genome. To determine when the amplification of FRG1 occurred, we used a PCR-based approach to identify F RG1 sequences from great apes, chimpanzee, gorilla and orang-utan, and an O ld 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 ch romosome 4q gene. This is strikingly similar to the distribution of a dispe rsed 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 th at an ancestral duplication of distal 4q included FRG1. This duplication is present in Macaca mulatta whose divergence from hominoids is thought to ha ve occurred at least 33 million years ago. We propose that this telomeric r egion then underwent further amplification and dispersion events in the gre at ape lineage, with copies of FRG1 and the 3.3-kb repeats being localized in heterochromatic regions. (C) 1999 Elsevier Science B.V. All rights reser ved.