THE DISTRIBUTION OF VARIATION IN REGULATORY GENE SEGMENTS, AS PRESENTIN MHC CLASS-II PROMOTERS

Diversity in the antigen-binding receptors of the immune system has lo ng been a primary interest of biologists. Recently it has been suggest ed that polymorphism in regulatory (noncoding) gene segments is of sub stantial importance as well. Here, we survey the level of variation in MHC class II gene promoters in man and mouse using extensive collecti ons of published sequences together with unpublished sequences recentl y deposited by us in the EMBL gene bank using the Shannon entropy to q uantify diversity. For comparison, we also apply our analysis to dista ntly related MHC class II promoters, as well as to class I promoters a nd to class II coding regions. We observe a high level of intraspecies variability, which in mouse but not in man is localized to a signific ant extent near the binding sites of transcription factors-sites that are conserved over longer evolutionary distances. This localization ma y both indicate and enhance heterozygote advantage, as the presence of two functionally different promoters would be expected to confer flex ibility in the immune response.