Importance of the matriline for genomic imprinting, brain development and behaviour

Abstract

Mammalian brain development commences during foeto-placental development and is strongly influenced by the epigenetic regulation of imprinted genes. The foetal placenta exerts considerable influence over the functioning of the adult maternal hypothalamus, and this occurs at the same time as the foetus itself is developing a hypothalamus. Thus, the action and interaction of two genomes in one individual, the mother, has provided a template for co-adaptive functions across generations that are important for maternal care and resource transfer, while co-adaptively shaping the mothering capabilities of each subsequent generation. The neocortex is complex, enabling behavioural diversity and cultural learning such that human individuals are behaviourally unique. Retrotransposons may, in part, be epigenetic mediators of such brain diversity. Interestingly some imprinted genes are themselves retrotransposon-derived, and retrotransposon silencing by DNA methylation is thought to have contributed to the evolutionary origins of imprint control regions. The neocortex has evolved to be adaptable and sustain both short-term and long-term synaptic connections that underpin learning and memory. The adapted changes are not themselves inherited, but the predisposing mechanisms for such epigenetic changes are heritable. This provides each generation with the same ability to make new adaptations while constrained by a transgenerational knowledge-based predisposition to preserve others.

Using next-generation RNA sequencing to identify imprinted genes

“…In animals, genomic imprinting is only known in therian mammals, and most imprinted genes are expressed and imprinted in the brain and placenta (Pask, 2012;Keverne, 2013;Renfree et al, 2013). Having the full catalog of imprinted genes in several different mammalian species will greatly facilitate the understanding of many evolutionary questions about genomic imprinting, including but not limited to origin and fixation of genomic imprinting, conservation of degree of expression direction and imprinted genes, dynamic gain and loss of imprinting status on the mammalian phylogenetic tree and effect of loss of diploidy for imprinted genes in shaping the population genetic profile.…”

Mammalian viviparity: a complex niche in the evolution of genomic imprinting

“…As the foetus is developing its own hypothalamus at this time period, a developmental template is available on which selection pressures may operate within a generation with functional consequences across two generations (Figure 2). Thus, an infant who has received optimal nourishment and care will itself be both energetically equipped and genetically predisposed to good mothering in the next generation (Keverne, 2012). Molecular genetic studies have identified several of the imprinted genes, which are co-expressed in the developing hypothalamus and placenta, to be concerned with regulation of maternal behaviour and physiology (Keverne, 2012).…”

“…Thus, an infant who has received optimal nourishment and care will itself be both energetically equipped and genetically predisposed to good mothering in the next generation (Keverne, 2012). Molecular genetic studies have identified several of the imprinted genes, which are co-expressed in the developing hypothalamus and placenta, to be concerned with regulation of maternal behaviour and physiology (Keverne, 2012). Detailed studies with mice carrying a mutation in the maternally imprinted gene (Peg3) have provided some insights into how the functioning of the hypothalamus, which develops in utero, is adapted to respond to the placental hormones that determine maternalism.…”

“…The convergent actions of Peg3 in mother and foetus illustrate its functional co-adaption for the hypothalamus and placenta. This developmental period (E11-12-13, mouse) is important for hypothalamic development and represents a period for major changes in transcriptional synchrony for the imprinted genes co-expressed in the hypothalamus and placenta (Keverne, 2012). Inactivation of the imprinted Peg3 genes both suppresses many downstream coexpressed genes, desynchronises placental and hypothalamic expression of others, and disrupts co-ordinated function of mother and foetus.…”

“…This hybridisation of placental and hypothalamic genes into a male Sry sex-determining gene has ensured critical in utero timing for the development of foetal leydig cells. Foetal leydig cell production of testosterone counteracts the maternalising influence of placental hormones and masculinises the male hypothalamus, an effect that continues into the early post-partum period when foetal leydig cells subsequently undergo apoptosis (Keverne, 2012).…”