Similar integration but different stability of Alus and LINEs in the humangenome

Alus and LINEs (LINE1) are widespread classes of repeats that are very unev enly distributed in the human genome. The majority of GC-poor LINEs reside in the GC-poor isochores whereas GC-rich Alus are mostly present in GC-rich isochores. The discovery that LINES and Alus share similar target site dup lication and a common AT-rich insertion site specificity raised the questio n as to why these two families of repeats show such a different distributio n in the genome. This problem was investigated here by studying the isochor e distributions of subfamilies of LINES and Alus characterized by different degrees of divergence from the consensus sequences, and of Alus, LINEs and pseudogenes located on chromosomes 21 and 22. Young Alus are more frequent in the GC-poor part of the genome than old Alus. This suggests that the gr adual accumulation of Alus in GC-rich isochores has occurred because of the ir higher stability in compositionally matching chromosomal regions. Densit ies of Alus and LINEs increase and decrease, respectively, with increasing GC levels, except for the telomeric regions of the analyzed chromosomes. In addition to LINEs, processed pseudogenes are also more frequent in GC-poor isochores. Finally, the present results on Alu and LINE stability/exclusio n predict significant losses of Alu DNA from the GC-poor isochores during e volution, a phenomenon apparently due to negative selection against sequenc es that differ from the isochore composition. (C) 2001 Elsevier Science B.V . All rights reserved.