Genes and environments, development and time

Abstract

A now substantial body of science implicates a dynamic interplay between genetic and environmental variation in the development of individual differences in behavior and health. Such outcomes are affected by molecular, often epigenetic, processes involving gene-environment (G-E) interplay that can influence gene expression. Early environments with exposures to poverty, chronic adversities, and acutely stressful events have been linked to maladaptive development and compromised health and behavior. Genetic differences can impart either enhanced or blunted susceptibility to the effects of such pathogenic environments. However, largely missing from present discourse regarding G-E interplay is the role of time, a "third factor" guiding the emergence of complex developmental endpoints across different scales of time. Trajectories of development increasingly appear best accounted for by a complex, dynamic interchange among the highly linked elements of genes, contexts, and time at multiple scales, including neurobiological (minutes to milliseconds), genomic (hours to minutes), developmental (years and months), and evolutionary (centuries and millennia) time. This special issue of PNAS thus explores time and timing among G-E transactions: The importance of timing and timescales in plasticity and critical periods of brain development; epigenetics and the molecular underpinnings of biologically embedded experience; the encoding of experience across time and biological levels of organization; and gene-regulatory networks in behavior and development and their linkages to neuronal networks. Taken together, the collection of papers offers perspectives on how G-E interplay operates contingently within and against a backdrop of time and timescales.

Keywords: biological embedding of experience; critical periods; gene regulation; gene–environment interplay; timing.

Fig. 1.

Pictoral representation of time scales in G–E interplay. (A) At the cellular level, the opening and closing of critical periods in brain plasticity act at the millisecond to second time scale (the parvalbumin-positive [PV] interneurons of the PV cell innervates the pyramidal neuron, the perineuronal net [PNN] gradually forms around PV cells) (45). (B) An experience of cocaine induces the expression of multiple IEGs in the mouse dorsal striatum; ∼40 Å images show expression of the following IEGs: Activity-regulated cytoskeleton-associated protein (Arc), early growth response 2 (Egr2), and nuclear receptor subfamily 4 group A member 1 (Nr4a1) in control vs. 1 h following acute cocaine (73). Reprinted from ref. . (C) Circadian clock genes generate circadian rhythms that affect many biological processes, including critical periods, sleep, metabolism, mood, and memory (45). (D) Critical periods in brain plasticity development are found within and across sensory, language, and higher cognitive domains. Image credit: Charles A. Nelson (Harvard University, Boston, MA). (E) Biological embedding of maternal stress in the developing fetus. (F) Transgenerational inheritance of trauma in grandchildren of holocaust survivors. (G) From an evolutionary time scale, the genome is a repository of changes in DNA sequence. Image credit: Sydney Gram (University of Toronto, Toronto, ON, Canada).