Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus

Previous studies have shown that the chloride channel gene Clc4 is X-linked and subject to X inactivation in Mus spretus, but that the same gene is autosomal in laboratory strains of mice, This exception to the conservation of linkage of the X chromosome in one of two interfertile mouse species was exploited to compare expression of Clc4 from the X chromosome to that from the autosome, Clc4 mas found to be highly expressed in brain tissues of both mouse species, Quantitative analyses of species-specific expression of Clc4 in brain tissues from mice resulting from M. spretus x laboratory strain crosses, demonstrate that each autosomal locus has half the level of CIc4 expression as compared with the single active X-linked locus. In contrast expression of another chloride channel gene, Clc3, which is autosomal in both mouse species is equal between alleles in F-I animals, There is no evidence of imprinting of the CIc4 autosomal locus, These results are consistent with Ohno's hypothesis of an evolutionary requirement for a higher expression of genes on the single active X chromosome to maintain balance with autosomal gene expression [Ohno, S. (1967) Sex Chromosomes and Sex-Linked Genes (Springer, Berlin)].