MOLECULAR CHARACTERIZATION OF A PERICENTRIC-INVERSION IN MOUSE CHROMOSOME-8 IMPLICATES TELOMERES AS PROMOTERS OF MEIOTIC RECOMBINATION

A ''hot spot'' of meiotic recombination has been found in males on murine chromosome 8 using nonisotopic hybridization of a series of probes to mitotic and meiotic chromosomes. The sequences responsible for this enhanced recombination are the telomeric repeats. Mice both normal and hetero- or homozygous for a pericentric inversion, In (8) 1 Rl, were analyzed. The inversion subdivides chromosome 8 into three discreet regions: (1) a fraction of the micro ''short arm'' that contains 30-150 kb of telomeric sequences and only about one-fifth of the contiguous minor-satellite sequences (approximately 200 kb); (2) the inverted region; and (3) the noninverted distal two-thirds of the chromosome. In 70 spermatocytes from inversion heterozygotes, examined by electron microscopy, synapsis of the inverted region was complete but entirely nonhomologous. Nonhomologous synapsis persists from initiation of synaptonemal complex formation in zygonema/early pachynema until dissolution in late pachynema. This non-homologous synapsis also suppresses crossing over within the inverted segment. The opportunity for proximal homologous recombination is thus restricted to the roughly 250 kb segment located between the short-arm break and the end of the bivalent. Nonetheless, an extreme proximal chiasma was observed in 11% of the heterozygous chromosome-8 bivalents, 34% of the normal 8 bivalents and 35% of the homozygous inversion 8 bivalents from spermatocyte preparations. Since in the normal chromosomes all minor satellite sequences are adjacent to the telomere, while in the inversion chromosomes most of these sequences are transposed to an interstitial position without a corresponding shift in chiasma position, the minor-satellite sequences can be ruled out as promoters of recombination. Instead, the data suggest that it is the telomeric sequences that promote recombination, not just within the telomeric repeat itself, but quite frequently in sequences more than 250 kb away.