THE EVOLUTION OF AN INTRON - ANALYSIS OF A LONG, DELETION-PRONE INTRON IN THE HUMAN DYSTROPHIN GENE

The sequence of a 112-kb region of the human dystrophin (DMD/BMD) gene encompassing the deletion prone intron 7 (110 kb) and the much shorte r intron 8 (1.1 kb) has been determined. Recognizable insertion sequen ces account for approximately 40% of intron 7. LINE-1 and THE-1/LTR se quences occur in intron 7 with significantly higher frequency than wou ld be expected statistically while Alu sequences are underrepresented. Intron 7 also contains numerous mammalian-wide interspersed repeats, a diverse range of medium reiteration repeats of unknown origin, and a sequence derived from a mariner transposon. By contrast, the shorter intron 8 contains no detectable insertion sequences. Dating of the L1 and Alu sequences suggests that intron 7 has approximately doubled in size within the past 130 million years, and comparison with the corres ponding intron from the pufferfish (Fugu rubripes) suggests that the i ntron has expanded some 44-fold over a period of 400 million years. Th e possible contribution of the insertion elements to the instability o f intron 7 is discussed. (C) 1997 Academic Press.