Abstract

Genes play a major role in controlling a wide range of biological, physiological and cellular processes. While the regulated level of expression of individual genes is known to play a key role in modulating specific cellular functions, genes however do not act in isolation. Instead, any individual cellular function is the result of a large number of genes acting in close coordination. In this study, we investigate the link between the relative level of gene expression or, alternatively, the level of co-ordination of functionally related genes (co-expression) and the level of demand for their associated biological function. Looking at mitosis genes, as defined by their Gene Ontology categorization, as a reference set of genes, we examined their expression and co-expression across tissue samples known to differ in their cell proliferation demands. Specifically, we looked at expression data from a variety of human-derived tissues including brain-derived samples at several developmental stages. Using microarray data, we compared highly proliferative cell lines with the much less proliferative nervous tissues and found that there was a significant decrease for both average expression and co-expression, of mitosis-associated genes, in line with decreased demand of proliferative functions. Co-expression, however, was a much stronger indicator of functional engagement. The observed contrast is not the result of comparing tumoural tissues with normal tissues as proliferative non-nervous tissues, showed significantly higher co-expression of mitosis genes than in nervous tissues. Using both microarray and RNA sequencing expression data, we compared average expression and co-expression of mitosis genes across pre-natal and post-natal brain-derived samples. In pre-natal development neurogenesis is higher as this is required for early formation of the brain, after birth this function is much less required. Our results show that absolute level of expression did not significantly alter, however co-expression of mitosis-associated genes was once again significantly higher during pre-natal development compared to post-natal stages. Our results show that co-expression is a robust signature of mitotic function requirement with average level of expression representing a less consistent predictor of functional activation. Whether this association between functional engagement and co-expression can be extended to all biological functions should be further investigated.