Heterozygote advantage for the phenylketonuria allele

Abstract

Mean weight at birth of unaffected (normal homozygous and PKU heterozygous) offspring of parents heterozygous for the phenylketonuria (PKU) allele averages significantly above that of Norwegian neonates, with no significant difference in mean age of mothers or in mean parity. It approaches the optimal birthweight, that which confers the minimum overall mortality in the pre, peri, and postnatal periods. This near optimal birthweight together with the possibly higher effective fertility observed in PKU heterozygous couples (at least in those who married before 1940), has apparently more than outweighed the disadvantages of the allelele in PKU homozygous offspring as shown, for example, in an excessive number of pre and perinatal deaths among the total offspring of PKU heterozygotes, to say nothing of the PKU survivors who, often, used to die young. The 2 effects, fertility and viability, apparently both contribute in the same direction, to give a biological fitness in excess of 1 for the heterozygote. This heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously lethal allele by mutation alone.