More about the. tabby mouse and about the Lyon hypothesis

Abstract

The Lyon hypothesis (L.H.) of dosage compensation of sex-linked genes in mammals postulates that in the female, during embryonic development and at the cellular level, either the paternal or the maternal X-chromosome is inactivated; that this inactivation happens at random; and that it persists in the descendants of the cell in which it has taken place. The genetic evidence hitherto adduced as favouring the L.H. has mainly involved complex situations such as the simultaneous segregation of two sex-linked genes and/or the behaviour of genes in structurally abnormal chromosomes. By contrast, this paper examines the behaviour of sex-linked genes in mammals (other than man) taken one at a time and in structurally normal X-chromosomes. Criteria are discussed by means of which the validity of the L.H. in such genetically simple situations can be tested. These tests reveal that the behaviour of heterozygotes for three sex-linked genes in the mouse (tabby, striated, brindled) is decisively at variance with the L.H., and the same is probably true for a fourth gene, bent-tail. The remaining sex-linked genes in the mouse give no evidence for or against the L.H. As there is thus clear evidence that in three, and probably in all four instances, both alleles are active as in ordinary autosomal heterozygotes, it is evident that in the mouse there is no inactivation of a whole Jf-chromosome. Indeed, the facts discussed in this paper (including those of one instance each in hamster, cattle and cat) do not suggest that there is any inactivation at all. Nonetheless there is a suspicion that heterozygotes for sex-linked genes, taken as a group, may include more cases of semi-dominance than occur in autosomal heterozygotes. If this should be substantiated, it would require an explanation.