Social regulation of human gene expression

Abstract

Relationships between genes and social behavior have historically been construed as a one-way street, with genes in control. Recent analyses have challenged this view by discovering broad alterations in the expression of human genes as a function of differing socio-environmental conditions. The emerging field of social genomics has begun to identity the types of genes subject to social regulation, the biological signaling pathways mediating those effects, and the genetic polymorphisms that moderate socio-environmental influences on human gene expression.

FIGURE 1

Social signal transduction. Socio-environmental processes regulate human gene expression by activating central nervous system processes that subsequently influence hormone and neurotransmitter activity in the periphery of the body. Peripheral signaling molecules interact with cellular receptors to activate transcription factors, which bind to characteristic DNA motifs in gene promoters to initiate (or repress) gene expression. Only genes that are transcribed into RNA actually impact health and behavioral phenotypes. Individual differences in promoter DNA sequences (e.g., the [G/C] polymorphism shown here) can affect the binding of transcription factors, and thereby influence genomic sensitivity to socio-environmental conditions.

FIGURE 2

Social regulation of gene expression in human immune cells. Expression of 22,283 human gene transcripts was assayed in 10 million blood leukocytes sampled from each of 14 older adults who showed consistent differences over 4 years in their level of subjective social isolation. 209 gene transcripts showed ≥ 30% difference in average expression level in leukocytes from 6 people experiencing chronic social isolation vs. 8 experiencing consistent social integration. In the heat-plot above, each row represents data from one of the 14 study participants, each column contains expression values for one of the 209 differentially active genes, and the coloring of each cell represents the relative level of that gene’s expression in a given participant’s leukocyte sample: Red = high expression, Black = intermediate expression, Green = low expression. (Adapted from Cole, et al., 2007).

FIGURE 3

RNA as a molecular medium of recursive development. Social conditions at one point in time (Environment₁) are transduced into changes in behavior (Behavior₁) and gene expression (RNA₁) via CNS perceptual processes that trigger systemic neural and endocrine responses (mediated by Body₁). Those RNA transcriptional dynamics may alter molecular characteristics of cells involved in environmental perception or response, resulting in a functionally altered Body₂. Body₂ may respond differently to a given environmental challenge that would the previous Body₁, resulting in different behavioral (Behavior₂) and RNA transcriptional responses (RNA₂). The persisting effect of RNA transcriptional dynamics on cellular protein and functional characteristics provides a molecular framework for understanding how socio-environmental conditions in the past may continue to affect current behavior and health, and how those historical conditions interact with current environments to shape our future trajectories (e.g., Body₃, Behavior₃, RNA₃). Because gene transcription serves as both a cause of social behavior (by shaping Body) and a consequence of social behavior (a product of Environment x Body), RNA can serve as the physical medium for a recursive developmental trajectory that integrates genetic characteristics and historical-environmental regulators to understand individual biological and behavioral responses to current environmental conditions.