Genomic sequence comparison of the human and mouse adenosine deaminase gene regions

A challenge for mammalian genetics is the recognition of critical regulator y regions in primary gene sequence. One approach to this problem is to comp are sequences from genes exhibiting highly conserved expression patterns in disparate organisms. Previous transgenic and transfection analyses defined conserved regulatory domains in the mouse and human adenosine deaminase (A DA) genes. We have thus attempted to identify regions with comparable simil arity levels potentially indicative of critical ADA regulatory regions. On the basis of aligned regions of the mouse and human ADA gene, using a 24-bp window, we find that similarity overall (67.7%) and throughout the noncodi ng sequences (67.1%) is markedly lower than that of the coding regions (81% ). This low overall similarity facilitated recognition of more highly conse rved regions. In addition to the highly conserved exons, ten noncoding regi ons >100 bp in length displayed >70% sequence similarity. Most of these con tained numerous 24-bp windows with much higher levels of similarity. A numb er of these regions, including the promoter and the thymic enhancer, were m ore similar than several exons. A third block, located near the thymic enha ncer but just outside of a minimally defined locus control region, exhibite d stronger similarity than the promoter or thymic enhancer. In contrast, on ly fragmentary similarity was exhibited in a region that harbors a strong d uodenal enhancer in the human gene. These studies show that comparative seq uence analysis can be a powerful tool for identifying conserved regulatory domains, but that some conserved sequences may not be detected by certain f unctional analyses as transgenic mice.