title: Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus.
abstract: 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 was 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 Clc4 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 F1 animals. There is no evidence of imprinting of the Clc4 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)].
authors.affiliation: Department of Pathology, Box 357470, University of Washington, Seattle, WA 98195-7470, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Adler
authors.forename: E I
authors.initials: EI
authors.lastname: Rugarli
authors.forename: P A
authors.initials: PA
authors.lastname: Lingenfelter
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: D
authors.initials: D
authors.lastname: Poslinski
authors.forename: H D
authors.initials: HD
authors.lastname: Liggitt
authors.forename: V M
authors.initials: VM
authors.lastname: Chapman
authors.forename: R W
authors.initials: RW
authors.lastname: Elliott
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: C M
authors.initials: CM
authors.lastname: Disteche
mesh_terms: D000818:Animals; D005075:Biological Evolution; D018118:Chloride Channels / Q000235:genetics*; D003433:Crosses, Genetic; D008040:Genetic Linkage; D051379:Mice; D015854:Up-Regulation; D014960:X Chromosome
chemical_list: D018118:Chloride Channels