RT Journal A1 Cowell, Lindsay G. A1 Kepler, Thomas B. A1 Janitz, Michael A1 Lauster, Roland A1 Mitchison, N. Avrion T1 The Distribution of Variation in Regulatory Gene Segments, as Present in MHC Class II Promoters JF Genome Research JO Genome Research YR 1998 FD February 01 VO 8 IS 2 SP 124 OP 134 DO 10.1101/gr.8.2.124 UL http://genome.cshlp.org/content/8/2/124.abstract AB Diversity in the antigen-binding receptors of the immune system has long been a primary interest of biologists. Recently it has been suggested that polymorphism in regulatory (noncoding) gene segments is of substantial importance as well. Here, we survey the level of variation in MHC class II gene promoters in man and mouse using extensive collections of published sequences together with unpublished sequences recently deposited by us in the EMBL gene bank using the Shannon entropy to quantify diversity. For comparison, we also apply our analysis to distantly related MHC class II promoters, as well as to class I promoters and to class II coding regions. We observe a high level of intraspecies variability, which in mouse but not in man is localized to a significant extent near the binding sites of transcription factors—sites that are conserved over longer evolutionary distances. This localization may both indicate and enhance heterozygote advantage, as the presence of two functionally different promoters would be expected to confer flexibility in the immune response.