HLA-G(∗)01:05N null allele in Mayans (Guatemala) and Uros (Titikaka Lake, Peru): evolution and population genetics.

Abstract HLA-G molecules seem to have a protective effect for the semi–allogeneic fetus by mother immunosuppression. Also, pregnancy pathologies have been associated to HLA-G ∗ 01:05N “null allele”. In addition, other general regulatory immune functions have been associated to HLA-G in infections, tumors and autoimmunity. Thus, it is striking that HLA ∗ 01:05N allele is maintained in a substantial frequency in certain human populations. In the present work, we have analysed HLA-G allele frequencies in Amerindian Mayans from Guatemala and in Uros from Titikaka Lake “totora” (reed) floating islands (Peru). No HLA-G ∗ 01:05N has been found in both of these Amerindian populations. Further studies in Worldwide populations show that the highest HLA-G ∗ 01:05 allele frequencies are found in Middle East; these findings have a bearing in future clinical/epidemiological studies in Amerindians. This would suggest that either this area was close to the “null” allele origin (as predicted by us) and/or some evolutive pressures are maintaining these high frequencies in Middle East. However, the fact that Cercopithecinae primate family (primates postulated as distant human ancestors) has also a MHC-G “null“ allele in all individuals suggests that this allele may confer some advantage either at maternal/fetal interface or at other immune HLA-G function level (tumors, infections, autoimmunity). Human HLA-G ∗ 01:05N may produce HLA-G isoforms, like Cercopithecinae monkeys may, which may suffice for function.