Intron sequences reveal evolutionary relationships among major histocompatibility complex class I genes.

The multigene family of the class I histocompatibility antigens is unusual in that allelic and intergenic differences often are of equal magnitude. It has been suggested that this is due to gene conversion events, which would produce allelic variation but at the same time reduce intergenic differences. We compared the sequences of 11 class I genes in an attempt to elucidate the evolutionary history of this gene family. Our analysis shows that the intron sequences can be used to establish the order of divergence of various class I genes from each other. The results obtained agree with the order of divergence deduced from major insertion and deletion events. It appears that certain genes in the murine TL antigen-encoding region diverged very early from the H-2 and Qa-2,3 genes. The latter can be subgrouped as H-2 and Qa-2,3 genes by both sequence homology and insertion patterns. In contrast to the introns, exon sequences provide less information on evolutionary relationships. Thus, these analyses are consistent with the view that concerted evolution due to gene conversion occurs preferentially in exons.