Evolution of the Human RH (Rhesus) Blood Group Genes: A 50 Year Old Prediction (Partially) Fulfilled

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Almost exactly 50 years ago, R.A. Fisher and R. Race proposed a model for the evolution of the RH (rhesus) genes in which the less common haplotypes were derived from the commoner ones by recombi nation, and in which the gene order was D-C-E. No direct evidence bearing on this model was available then, and has not been until now. Here we present evidence for non-reciprocal intergenic exchange (gene conversion) occurring once in human history to generate the common RHCE allele, Ce. We have also used new polymorphisms to construct haplotypes which suggest that intragenic recombination played a major role in the generation of the less common haplotypes, but only if RHD lies 3′ of RHCE, i.e. the order is C-E-D. We provide both genetic and physical evidence supporting this arrangement.