Evolutionary history of linked D4Z4 and Beta satellite clusters at the FSHD locus (4q35)

We performed a detailed genomic investigation of the chimpanzee locus syntenic to human chromosome 4q35.2, associated to the facioscapulohumeral dystrophy. Two contigs of approximately 150 kb and 200 kb were derived from PTR chromosomes 4q35 and 3p12, respectively: both regions showed a very similar sequence organization, including D4Z4 and Beta satellite linked clusters. Starting from these findings, we derived a hypothetical evolutionary history of human 4q35, 10q26 and 3p12 chromosome regions focusing on the D4Z4-Beta satellite linked organization. The D4Z4 unit showed an open reading frame (DUX4) at both PTR 4q35 and 3p12 regions; furthermore some subregions of the Beta satellite unit showed a high degree of conservation between chimpanzee and humans. In conclusion, this paper provides evidence that at the 4q subtelomere the linkage between D4Z4 and Beta satellite arrays is a feature that appeared late during evolution and is conserved between chimpanzee and humans.

► A detailed genomic analysis of the PTR locus syntenic to human chromosome 4q35.2. ► PTR 4q35 and 3p12 regions carried a very similar D4Z4 and Beta satellite linked clusters. ► We derived a presumable evolutionary history of human 4q35, 10q26 and 3p12 regions. ► PTR and HSA subregions of the Beta satellite showed a high degree of conservation. ► 4q D4Z4-Beta satellite linked arrays appeared very late during evolution.