Knowledge Base

Environmental Signaling

When the sequence of the human genome was announced in 2000, there was great hope that biological science could find a gene responsible for predicting health and disease outcomes in humans {Collins, 2004}. However, it soon became apparent that the environment interacting with human genes played a pivotal role in mediating gene actions {Gilbert, 2000}. The environment in which people live has a strong influence on whether a health or disease phenotype is expressed.

The environment around the gene is not easy to define or study. The environment with which genes interact is known as the exposome {Nakamura, 2014; Wild, 2012}. The exposome includes nutrients, noise, occupation, psychosocial environment, social economic status and education as well as pollutant chemicals, microorganisms, drugs, food, and additives {Wild, 2012}. The exposome includes social environment as one aspect of the pathway to disease. Wild divided the exposome into three parts:

  • general external environment
  • internal environment
  • the specific external environment

The general external environment includes social capital, education, social economic status, and where you live. The internal environment is comprised of metabolism, endogenous hormones, microbial flora, physical activity, and oxidative stress. The specific external environment includes chemical pollutants; infectious agents and lifestyle exposures, such as alcohol and tobacco use {Wild, 2012}. Therefore, the paradigm of [ exposure → physiological change → disease ] while still true, is more complex than previously thought.

Environmental Signaling

Figure 1. A Conceptual Design of Environmental Signaling Pathways (click here for a detailed and referenced model)

Human homeostasis is a process tightly regulated by interacting signaling pathways. When things in the cellular environment change, cells and organisms respond.  Signaling within the exposome demonstrates converging signals. In some cases, an environmental chemical is itself the signaling molecule. In others, an environmental factor stimulates internal signaling systems, and in others, psychosocial factors or trauma conveys signals to an organism. Thus, the signals elicit a functional change in the cell or organism {McLachlan, 2016}. The functional changes are often through epigenesis.

Epigenetics is the study of heritable changes in gene-expression that occur without changes in DNA sequence {Ekström, 2009}. Epigenesis is the biochemical process underlying changes in gene-expression that occur without a change in DNA sequence by activating or silencing specific genes in response to an environmental signal {Combs-Orme, 2013}. The environment around the genotype is most critical in determining health phenotype. Epigenesis has provided evidence that the genotype cannot predict the exact phenotype but rather phenotype is controlled by the environment in which the genotype is expressed.



Collins, F. The case for a US prospective cohort study of genes and environment. Nature (London) 2004, 429, 475-477

Gilbert, S. F., Sarkar, S. Embracing Complexity: Organicism for the 21st century, Dev. Dynamics, 2000, 219, 1-9

Nakamura, J.; Mutlu, E.; Sharma, V.; Collins, L.; Bodner, W.; Yu, R.; Lai, Y.; Moeller, B.; Lu, K.; Lai, Y.; Moeller, B.; Lu, K.; Swenberg, J. The endogenous exposome. DNA Repair (Amst) 2014, 19, 3-13

Wild, C.P. The exposome: From concept to utility. Int. J. Epidemiol. 2012, 41, 24- 32

McLachlan, J. A. Environmental Signaling: from environmental estrogens to endocrine -disrupting chemicals and beyond, Andrology, 2016, 1-11

McLachlan, J. A. Environmental Signaling: What Embryos and Evolution Teach Us About Endocrine Disrupting Chemicals. Endocrine Reviews 22 (3): 319-41, 2001

Ekström, T.J. Epigenetic control of gene expression. BBA -General Subjects 2009, 1790,845-846

Combs-Orme, T. Epigenetics and the social work imperative. Soc. Work 2013, 58, 23-30