Molecular studies of the human x and y chromosomes
The isolation and characterisation of sequences from the X and Y chromosomes will give some insight into the evolutionary relationship between these chromosomes, and may be of use in the study of X-linked disorders. The availability of cDNA and genomic sequences for the human STS locus (associated with the disorder, X-linked ichthyosis) has allowed a preliminary investigation of this locus in man and other species. The localisation of these sequences to Xp22.3, provides confirmation of the sub-regional assignment of the structural gene for STS. STS homologous sequences have been identified on the long arm of the Y chromosome. These sequences also appear present on the X and Y chromosomes of the chimpanzee. In other higher primates, they appear to be X-, but not Y-, linked, suggesting that the situation in man and chimpanzee is the result of a rearrangement between the X and Y chromosomes during the past 15 million years. Another region of X Y homology has been analysed. The locus DXYS27 maps to Yp and Xq21. Restriction enzyme analysis and direct sequence comparison has shown the two loci to be «99% homologous. Phylogenetic studies suggest that the locus is X-, but not Y-, linked in the chimpanzee, suggesting an evolutionarily recent transposition of material from the X to the Y chromosome. The mutations resulting in the X-Y differences appear to have occurred on both the X and Y chromosomes. It has been possible to demonstrate that the Y-specific locus is transferred to the X chromosome in many, but not all, aberrant X-Y interchanges resulting in XX maleness. A sequence has been isolated that detects a hypervariable locus at Xp11.3→Xcen (DXS255) . The hypervariability appears to be due to the presence of a tandemly repeated sequence of variable length. Attempts to clone this repeat have been unsuccessful, as it appears to be unstable in the vector/host systems employed. This sequence will be of value in linkage studies of disease loci known to be present in this region. Hypervariability at this locus has not been identified in other species, suggesting that the repeat sequence is an evolutionarily recent acquisition by the X chromosome. Taken together, the results obtained suggest that the simple model predicting an ancient origin for the bulk of the Y chromosome will have to be reassessed.