Of cardiovascular illness and diversity of biological response

Abstract

Noise in gene expression (stochastic variation in the composition of the transcriptome in response to stimuli) may play an important role in maintaining robustness and flexibility, which ensure the stability of normal physiology and provide adaptability to environmental changes for the living system. Broad-based technologies have allowed us to study with unprecedented accuracy the molecular profiles of various states of health and cardiovascular disease. In doing so, we have observed a correlation between the degree of variation in gene expression and the state of health. Specifically, the stochastic variation in gene expression in response to environmental and physiological factors is found in healthy mice, and tends to disappear in mice with advanced disease states. Although further evidence is needed to draw a solid conclusion with respect to the significance of decreased transcriptional noise in the disease state as a whole, it is tantalizing to introduce the concept that stochasticity may be linked to the organism's adaptability to a changing environment, and the "quiet" states of gene expression may indicate the loss of diversity in the organism's response.

Figure 1

Gene expression predictors of aortas from apoE^−/− and WT mice of different ages. Rows depict standardized expression of genes across samples (columns). Blue represents relatively lower expression compared with red (higher expression).

Figure 2

Color map illustrating the composite genome wide gene expression variability of the aortas from wild type and apoE knockout mice. With increasing disease in the apoE mice, there is a decrease in gene expression variability.