A highly divergedβ1 exon in theDR region of the human MHC: Sequence and evolutionary implications
Tóm tắt
TheDR subregion of the human major histocompatibility complex from aDR4 haplotype includes the well-characterizedDR
ga
,DR4
β
DR(MT3)
βandDR
βψgenes. In addition, the region between theDR
αand the proximalDR(MT3)
βgenes contains several copies of conserved DR
β
-related sequences. These repeated elements, numbered II, III, and IV, include the DR
β
signal sequence and a region located further upstream. Further examination of these conserved sequences showed that DR
β
first intron sequences are present at the 3′ ends of these repeats. Progressively longer portions of the DR
β
first intron are conserved from repeat II to repeat IV, producing a gradient of conservation. The most complete repeat element of repeats II, III, and IV is associated with a loneβ1 exon (DR
β1). Upon sequencing, (DR
β1). was found to contain several deleterious mutations, indicating that it is nonfunctional. (DR
β1). has accumulated a large number of replacement substitutions and mutations at positions which are invariant inβ1 domains from expressedDR
βgenes: 77.8% of the nucleotide substitutions were replacement substitutions, and 41.5 % of the amino acids at invariant positions have been altered. Calculations based on these figures suggest thatDR
β1 may have become inactive approximately 25 million years ago. There are, however, two histidine residues within a variable region which are unique toDR
β1 and theDR4
βgene, suggesting that they represent a gene pair which probably evolved by duplication of a singleDR
βchain gene.
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