Evolution of genomic imprinting with biparental care: implications for Prader-Willi and Angelman syndromes.

The term "imprinted gene" refers to genes whose expression is conditioned by their parental origin. Among theories to unravel the evolution of genomic imprinting, the kinship theory prevails as the most widely accepted, because it sheds light on many aspects of the biology of imprinted genes. While most assumptions underlying this theory have not escaped scrutiny, one remains overlooked: mothers are the only source of parental investment in mammals. But, is it reasonable to assume that fathers' contribution of resources is negligible? It is not in some key mammalian orders including humans. In this research, I generalize the kinship theory of genomic imprinting beyond maternal contribution only. In addition to deriving new conditions for the evolution of imprinting, I have found that the same gene may show the opposite pattern of expression when the investment of one parent relative to the investment of the other changes; the reversion, interestingly, does not require that fathers contribute more resources than mothers. This exciting outcome underscores the intimate connection between the kinship theory and the social structure of the organism considered. Finally, the insight gained from my model enabled me to explain the clinical phenotype of Prader-Willi syndrome. This syndrome is caused by the paternal inheritance of a deletion of the PWS/AS cluster of imprinted genes in human Chromosome 15. As such, children suffering from this syndrome exhibit a striking biphasic phenotype characterized by poor sucking and reduced weight before weaning but by voracious appetite and obesity after weaning. Interest in providing an evolutionary explanation to such phenotype is 2-fold. On the one hand, the kinship theory has been doubted as being able to explain the symptoms of patients with Prader-Willi. On the other hand, the post-weaning symptoms remain as one of the primary concern of pediatricians treating children with Prader-Willi. In this research, I reconcile the clinical phenotype of Prader-Willi syndrome with the kinship theory, contending that paternal investment relative to maternal investment increases after weaning. I also propose a genetic composition of the PWS/AS cluster, discuss the effects of new types of mutations, and contemplate the potential side effects of reactivating silent genes for medical purposes.