Polymorphism and evolution of the Rh blood groups

Abstract

With the aim of understanding the mechanism of maintenance of the Rh polymorphism in man, the probability and the first arrival time of an incompatibility mutant allele (recessive allele r) to reach a high frequency by genetic drift in a finite population and the allele frequency distribution under mutation pressure are studied. The deterministic changes in allele frequency in subdivided populations are also studied. The results obtained are as follows: (1) If the effective population size is 500-1,000, the probability of a single mutant allele to reach a frequency of 0.3 or 0.5 is quite small, and without recurrent mutation it is unlikely that the mutant allele becomes polymorphic. However, if the mutant allele happens to increase in frequency by genetic drift, the increase occurs quite rapidly. (2) In an infinitely large population the backward (u) and forward mutations (v) produce two stable equilibria, one of which has a frequency of 0.065 for h=0.05 and a frequency of 0.16 for h=0.01 when u=v=10^-4, where h is the fitness reduction for the offspring from mating rr×RR. These frequencies are substantially higher than 0 but still lower than the frequencies in the European populations (0.3-0.6). In relatively small populations, however, the probability of the allele frequency being 0.3-0.6 becomes quite high if h=0.01. (3) If a population is subdivided into subpopulations among which small migration occurs, stable equilibria may be developed. However, the equilibrium gene frequencies do not conform to the frequencies observed in the European populations. When the migration rate becomes higher, the stable equilibria disappear, but the gene frequency change in subdivided populations is generally much slower than that in a single random mating population, so that the Rh polymorphism may be maintained for a long time even if there are no stable equilibria. (4) If we consider all these factors together, it is possible to explain the Rh polymorphism in terms of the mutation-drift hypothesis without recourse to reproductive compensation. It seems that the Rh polymorphism is transient rather than stable.