RAPID EVOLUTION OF HUMAN PSEUDOAUTOSOMAL GENES AND THEIR MOUSE HOMOLOGS

Comparative studies of genes in the pseudoautosomal region (PAR) of hu man and mouse sex chromosomes have thus far been very limited. The onl y comparisons that can presently be made indicate that the PARs of hum ans and mice an not identical in terms of gene content. Here we descri be additional comparative studies of human pseudoautosomal genes and t heir mouse homologs. Using a somatic cell hybrid mapping panel, we hav e assigned the mouse homolog of the human pseudoautosomal interleukin 3 receptor alpha subunit (IL3RA) gene to mouse Chromosome (Chr) 14. At tempts to clone the mouse homolog of the human pseudoautosomal adenine nucleotide translocase-3 (ANT3) gene resulted in the isolation of the murine homologs of the human ANT1 and ANT2 genes. The mouse Anti and Ana genes are very similar in sequence to their human homologs, and we have mapped them to mouse Chromosomes (Chrs) (8 and X respectively) t hat exhibit conserved synteny with the chromosomes on which the human genes are located. In contrast, the homolog of ANT3 appears to be eith er very divergent or absent from the mouse genome. Southern blot analy sis of DNA from a variety of mammalian spe cies shows restricted conse rvation of human pseudoautosomal genes, a trend that also applies to t he two cloned mouse homologs of these genes and to neighboring human g enes in distal Xp22.3. Our observations combined with those of other w orkers lead us to propose a model for the evolution of the PAR that in cludes both rapid sequence evolution and the incremental reduction in size of the region during mammalian evolution.