The secretor gene, which determines secretion of the ABH blood group antigens into saliva and other fluids, has widely varying frequencies in different healthy populations. Its frequency in patients suffering from certain diseases also differs from that in healthy persons. These observations suggest that frequencies of the gene are to some extent the results of natural selection.
One means of selection is through haemolytic disease of the newborn. Women, mostly of group O, become immunized to the A or B antigen of a fetus, and this or subsequent fetuses are at risk from haemolytic disease of the newborn. Affected fetuses are preponderantly secretors; this is probably a genetic consequence of all or most immunizing fetuses being secretors. Selection against the secretor factor as well as against blood groups A and B is thus liable to occur. Similar processes of selection seem to operate through fetal loss by early abortion. It is suggested that counter-selection favouring secretors may result from certain epidemic infectious diseases.
A two-selective forces model () has been proposed as beiong responsible for the consistent rate of ABO distribution. The first is generated by the invasion of opportunistic bacterial or other pathogens that interact with the epithelial-mucosal surfaces. The bacteria adapt to the microenvironments of common host phenotypes and so create frequency-dependent selection for rarer host alleles. The second is gener- ated by intracellular viruses, and accounts for the observed differentials between the ABO-phenotype frequencies. It is thought that viruses acquire histo-blood group structures as part of their envelope from their previous host. The presence of host antigens on the viral envelope causes differential transmission of the virus between host types owing to the asymmetric action of ABO natural antibodies. Our model simulations show that these two forces acting together can account for the major features of the ABO polymorphism in humans.
ABO evolution. Evolution of O (solid line), A (up-triangles), B (down-triangles) and AB (dashed line) phenotype frequencies under the influence of (a) bacteria alone and (b) bacteria and virus. The simulations use the bacterial parameters m = 2 and 3m = 0.02 and the viral transmission rate 3 = 0.1. Other parameter values are as in figures 1 and 2
Simulations suggest that both opportunistic bacterial infection and differential viral transmission are needed to account for the observed histo-blood group fre- quency distribution. With only the bacteria, a stable equi- librium is reached with higher frequencies of the A and B phenotypes than of the O phenotype. Although some populations have such a pattern, it is very common to find populations where O is the predominant phenotype. With only the virus, the O phenotype alone persists as the spread of the O allele causes the elimination of the A and B alleles. However, once both forces are combined, a range of phenotype frequencies is possible depending on the relative strength of bacterial and viral selection. If the bacterial force is stronger, A and B phenotypes are most frequent, whereas if the viral force is stronger, the O many isolated island populations have high O phenotype frequencies, from 54% to 100%, with correspondingly low A, B and AB frequencies.