Annual Review of Immunology Volume 8 1990 by Annual Reviews

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Locus-Specific Substitutions in HLA-A, B, C Genes May Result from Homogenization by Allelic Conversion Exons4-8 of HLA-A,B, C genes are highly conservedwithin alleles of a locus but exhibit significant diversificationbetweenloci. Thecritical question is whetherthe locus-specific substitutions are the result of positive selection or genetic drift. This could explain the 26 replacementsubstitutions, but it cannotaccountfor the 25 locus-specificsilent substitutions in exons 4-8 (45). Of particular interest is exon4 encodingthe ~3 domainin which 13 of the 17 locus-specificsubstitutionsare silent.

That analogouspatterns have been seen with all the ChLA-A, B, C alleles examinedprovides goodevidence for a gradual transspecies modeof evolution (45, 80, 81). Anotherapproachto this question is to compareall HLA-A,B, C and ChLA-A,B, C sequences to a consensus sequence, and to calculate the proportion of substitutions from that consensussequenceshared by the twospecies. 3%,are found in at least one HLA-A,B, C sequence. Assuming a common origin for the identical substitutions wecan estimate that less than 20%of the substitutions found in contemporaryHLAA, B, C molecules have been formed since divergence of humansand chimpanzees(45).

For personal use only. QS~ D~ rl LalOb I ~ ~ RT1A a ~ Klb RAT b na TI~ Figure 8 PAUPtrees }Q for the alleles RT1Aa } RAT Tla of the murine H-2, Qa and TI loci. b Tla b T3 Tla Panel A represents the tree for the entire exonic sequence. Gaps were inserted in exon 5 and in some of the nonclassical genes to produce an optimal alignment for this parsimony analysis. Panel B shows the relationships observed when only exons 1-4 are included in the analysis. conserved3’ exons(4-8) by the long intron betweenexons3 and 4 (29, 36).

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