ANCIENT, HIGHLY POLYMORPHIC HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX DQA1 INTRON SEQUENCES

A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 6 9 individuals from wide ethnic backgrounds. In contrast, the most vari able coding region spanned by the 247 basepair exon 2 defined 11 allel ic variants. Our phylogenetic human intron 1 tree derived by the Boots trap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1-10 , 1989]. Thus 3' DQA1 intron 1 and exon 2 have cosegregated since dive rgence of the human races. Comparison of human alleles to a Rhesus mon key DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolution ary stability of intron sequences since these two species diverged ove r 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typ ing for transplantation, paternity testing, and forensics and to deriv e more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource. (C) 1994 W iley-Liss, Inc.