摘要：Recent analyses have discovered broad alterations in the expression of human genes across different social environments. The emerging field of social genomics has begun to identify the types of genes sensitive to social regulation, the biological signaling pathways mediating these effects, and the genetic polymorphisms that modify their individual impact. The human genome appears to have evolved specific “social programs” to adapt molecular physiology to the changing patterns of threat and opportunity ancestrally associated with changing social conditions. In the context of the immune system, this programming now fosters many of the diseases that dominate public health. The embedding of individual genomes within a broader metagenomic network provides a framework for integrating molecular, physiologic, and social perspectives on human health. The conceptual relationship between genes and the social world has shifted significantly during the past 20 years. As genes have come to be understood in concrete molecular terms, rather than as abstract heritability constructs, it has become clear that social factors can play a significant role in regulating the activity of the human genome. DNA encodes the potential for cellular behavior, but that potential is only realized if the gene is expressed—if its DNA is transcribed into RNA ( Figure 1 ). RNA and its translated proteins are what mediate cellular behaviors such as movement, metabolism, and biochemical response to external stimuli (e.g., neurotransmission or immune response). Absent their expression in the form of RNA, DNA genes have no effect on health or behavioral phenotypes. The development of DNA microarray and high-throughput RNA sequencing technologies now allows researchers to survey the expression of all human genes simultaneously and map the specific subset of genes that are active in a given cell at a given point in time—the RNA “transcriptome.” 1 “Functional genomics” studies surveying RNA transcriptomes have shown that cells are highly selective about which genes they express, and humans’ DNA encodes a great deal more genetic potential than is actually realized in RNA. Even more striking has been the discovery that the social world outside one’s body can markedly influence these gene expression profiles. Open in a separate window FIGURE 1— Social signal transduction. Note . Socioenvironmental conditions 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 have an impact on 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 socioenvironmental conditions. This article reviews the emerging field of human social genomics, including its recent scientific development, some developing themes regarding the number and nature of “socially sensitive” genes, and emerging data on the psychological, neural, and endocrine signaling pathways that mediate social influences on gene expression. The presentation also considers some evolutionary theories regarding the teleology of such “social signal transduction” and the implications of these dynamics for environmental programming of human development and life-span health trajectories. The role of gene polymorphisms (genetics) in modulating individual genomic sensitivity to socioenvironmental influences is considered, as are implications of social genomic relationships for public health and policy, including optimal intervention strategies, new opportunities for integrating social genomics into epidemiology, and implications of a public health perspective for understanding how individual human genomes cross-regulate one another in the context of social networks (i.e., social regulation of the human “metagenome,” or the collective system of individual human genomes). Social genomics research provides a concrete molecular framework for understanding the long-observed relationship between social conditions and the distribution of human health and disease. 2–4
