The Significance of Genomic Imprinting for Brain Development and Behaviour

Professor Barry Keverne FRS, FMedSci – Behavioural Neuroscience, King's College, Cambridge, described how genomic imprinting provides for co-adaptation of mother and fetus, for maternal provision and fetal use of resources. On the other hand it is open to genetic transmission of clinical disorders, for instance Prada-Willli syndrome leading to obesity, and Angelman's syndrome with mental retardation. Among vertebrates, genomic imprinting only evolved in mammals and the placenta is a primary target for expression of imprinted genes. There are certain autosomal genes in mammals that are only expressed if inherited from one parent rather than from the other. More often the paternal gene – allele – is expressed which means that the maternal allele is silenced, usually by methylation, bonding of a CH3 group. Genomic imprinting, distinct from epigenesis, occurs in germ-line cells, ensuring transgenerational effects. Epigenesis, in somatic cells, is usually restricted to one generation, although if it causes a change of behaviour – better mothering say – that can have consequences in the next generation by social transmission. Imprinting is reversible according to parent of origin and there is no change in the gene sequence, as occurs by mutation. Genomic imprinting acts primarily through key regulatory genes which in turn have a cascade effect through other genes. Possible effects vary widely, for instance the mother's food intake and weight gain; maternal fat and blood glucose; letdown of milk and post-natal pup growth. Other affects include her maternal behaviour, nest-building, and placental hormones, placental blood flow and nutrient transfer, fetal growth, and early weaning and puberty onset. In these ways the placenta enables the fetus to regulate its own destiny, mainly by genomic co-adaptation affecting hormonal action on receptors in the maternal hypothalamus. The two genomes, infant and maternal, are co-adaptive for infant wellbeing and reproductive success. Offspring that have extracted “good” maternal nurturing through imprinted genes will themselves be genetically predisposed towards good mothering. Through imprinting, a gene contributing to fitness is established in the population more quickly, especially when paternally expressed due to the greater reproductive fitness of males expressing this allele. Although genomic imprinting affects hormonal activity and nutrient metabolism, there is no evidence for hormones or nutrients affecting genomic imprinting. Hormones and nutrients can, particularly in early life, epigenetically affect the individual's future life for better or for worse, and significantly contribute to “foetal programming”.