HALDANES RULE AND HETEROGAMETIC FEMALE AND MALE-STERILITY IN THE MOUSE

Failed genetic experiments or experiments designed for other purposes sometimes reveal novel genetic information. The interspecific cross be tween laboratory strain mice of the Mus musculus musculus/domesticus c omplex and the separate species M. spretus is known to produce fertile F-1 females and sterile F-1 males. Infertility of the interspecific F -1 XY male is said to be an example of what has become known as Haldan e's rule: ''When in the F-1 offspring of two different animal races on e sex is absent, rare, or sterile, that sex is the heterozygous [heter ogametic] sex.'' We attempted to use fertile single-X (or XO) female l aboratory mice of the M. m. musculus/domesticus complex mated to M. sp retus males to construct females with specific X chromosomes to study segregation distortion of X chromosome marker genes that we reported p reviously in crosses with the two species. We assumed that the intersp ecific F-1 XO female would be fertile like the interspecific F-1 XX fe male but, instead, we found that it is infertile. Haldane's rule is no t specific to sex, but demonstration of this has required study of sep arate species pairs with heterogametic males or with heterogametic fem ales. The fertile XO laboratory mouse is female, but it is also hetero gametic, producing both X and nullo-X eggs. Infertility of both the in terspecific and heterogametic F-1 XO female and F-1 XY male in the sam e cross between laboratory mice and M. spretus suggests that heterogam ety is at the cause of the infertility. The most parsimonious interpre tation is that there is an interaction between the single X and hetero zygous or heterospecific autosomes that may affect the same fundamenta l step in both female and male meiosis in the interspecific F-1 hybrid . This hypothesis is now testable in the mouse.