Type 2 diabetes: The genetic conflict hypothesis

Abstract We propose that conflict between paternally and maternally derived genes in the fetus explains three apparently unrelated observations in epidemiological studies of type 2 diabetes mellitus (DM2): (i) low birth weight is a risk factor for the development of DM2, (ii) there is a high prevalence of low birth weight among babies of fathers who develop DM2, and (iii) an exceptionally high prevalence of DM2 exists in modern day Arabs. Genetic conflict is caused by a particular relationship between the parents, their genes and their offspring: (i) mothers are sometimes polyandrous i.e. have children with more than one man, (ii) mothers provide more biological resources to the fetus than fathers, and (iii) the genes that regulate fetal growth come from both parents and both sets of genes determine the use of resources which are only those of the mother. There is a tendency for maternally derived genes (that promote fetal growth) to be suppressed, in order to spare use of mother’s resources, while the same paternally derived genes tend to be expressed (to enhance use of the mother’s resources). These same genes are pleiotropic: they affect not only fetal growth (birth weight) but also insulin resistance and hence the development of DM2. Polyandry increases differences in the expression between two parental alleles in the fetus i.e. increases genetic conflict and results in the production of bigger babies whereas monandry has the opposite effect. Consequently, parent-of-origin-biased expression of pleiotropic developmental genes could explain why smaller babies are more common when the fathers have DM2. Similarly less genetic conflict in Arabs (resulting from the tradition of strict monandry, the practice of levirate, and preference for a paternal cousin as spouse) could explain, at least in part, their exceptionally high prevalence of DM2. This hypothesis links human mate selection with the risk of developing DM2.