Nature 290, 68 - 70 (05 March 1981); doi:10.1038/290068a0

Recombination suppression of mouse t-haplotypes due to chromatin mismatching

Lee M. Silver^* & Karen Artzt

Sloan-Kettering Institute for Cancer Research, New York, New York 10021, USA
^*Present address: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

We show here that recombination occurs at the normal rate in compound female mice containing two different complementing lethal haplotypes (t ^h17/t ^w12 where there is a long stretch of homologous t-mutant chromatin. Thus the recombination suppression of a complete t-haplotype cannot be due to an intrinsic factor(s) which suppresses along the length of its own chromosome but is due to 'mismatching' of wild-type and mutant chromatin. Naturally occurring t-haplotypes of mouse chromosome 17 have several interesting genetic properties. First, they are always transmitted from males in much higher proportions than mendelian expectation; presumably this accounts for the maintenance of lethal and semilethal t-haplotypes at polymorphic levels in populations of wild mice, t-Haplotypes also show recombination suppression. The conventional map distance between genetic markers T and tf is 7−12 cM, whereas in (t/+) heterozygotes for naturally occurring t-haplotypes, recombination is suppressed and T and tf seem to be separated by only 0.1−0.5 cM (ref. 1). The region of recombination suppression extends to and includes the major histocompatibility complex (H−2)². Thus t and H−2 effectively travel as a single unit— a 'super gene'³. Although recombination suppression is known to be accompanied by failure of chiasmata formation⁴, the mechanism underlying the suppression has remained an enigma. Lyon suggested a disorder of t-heterochromatin⁵ and more recently a change in 'intercalary' middle repetitive DNA⁶. She proposed that either t-chromatin is intrinsically incapable of participating in crossing-over, or chiasma formation is prevented because of mismatching and mispairing of normal and abnormal chromatin. We have measured recombination between two chromosomes which carried extensive overlapping segments of t-chromatin. We report here that in this configuration, recombination occurs at a normal rate, and thus we conclude that cross-over suppression is due to mismatching.