Molecular clock and recombination in primate Mhc genes

To set an accurate chronological framework to the evolution of primate clas s I and II genes in the major histocompatibility complex (Mhc), the rate of silent nucleotide substitutions in exons and introns is examined for vario us cDNA and genom sequences currently available. The rate is sensitive to t he GC content and correlates negatively with increased GC biases at the thi rd codon positions of Mhc genes. The intergenic recombination rate in the H LA region is estimated from the synonymous nucleotide differences at 37 lin ked loci. Any HLA subregion is recombined more or less at the ordinary rate of 1 cM per 1 Mb, although the rate may be reduced in some subregions. Thi s information is used to discuss HLA haplotypes when they are applied to st udies of human demography. The unusual polymorphism in the alpha-helix of H LA-DRB1 is also revisited in relation to intragenic recombination, but the molecular mechanism and the evolutionary cause both remain enigmatic.