Academic journal article Genetics

Impact of Transcriptional Properties on Essentiality and Evolutionary Rate

Academic journal article Genetics

Impact of Transcriptional Properties on Essentiality and Evolutionary Rate

Article excerpt

ABSTRACT

We characterized general transcriptional activity and variability of eukaryotic genes from global expression profiles of human, mouse, rat, fly, plants, and yeast. The variability shows a higher degree of divergence between distant species, implying that it is more closely related to phenotypic evolution, than the activity. More specifically, we show that transcriptional variability should be a true indicator of evolutionary rate. If we rule out the effect of translational selection, which seems to operate only in yeast, the apparent slow evolution of highly expressed genes should be attributed to their low variability. Meanwhile, rapidly evolving genes may acquire a high level of transcriptional variability and contribute to phenotypic variations. Essentiality also seems to be correlated with the variability, not the activity. We show that indispensable or highly interactive proteins tend to be present in high abundance to maintain a low variability. Our results challenge the current theory that highly expressed genes are essential and evolve slowly. Transcriptional variability, rather than transcriptional activity, might be a common indicator of essentiality and evolutionary rate, contributing to the correlation between the two variables.

EVOLUTION of gene expression, which has long been a subject of great interest (KING and WILSON 1975), is now being studied on a genomic scale with the help of rapidly growing microarray and genome sequence data (ENARD et al. 2002; OLEKSIAK et al. 2002; MEIKLEJOHN et al. 2003; RANZ et al. 2003; RIFKIN et al. 2003; KHAITOVICH et al. 2004; DENVER et al. 2005). Of particular importance, expression level has been believed to be the best indicator of the evolutionary rate of encoded proteins. Highly expressed genes were found to evolve slowly from bacteria to mammals (SHARP 1991; DURET and MOUCHIROUD 2000; PAL et al. 2001; HERBECK et al. 2003; URRUTIA and HURST 2003; SUBRAMANIAN and KUMAR 2004; DRUMMOND et al. 2005). In addition, it has recently emerged as a governing factor behind the apparent relationships between evolutionary rate and other important genomic features. Specifically, the influences of protein-protein interactions and dispensability on evolutionary rate have been disputed on the grounds that their effects may be confounded with gene expression level (HIRSH and FRASER 2001; FRASER et al. 2002; BLOOM and ADAMI 2003; PAL et al. 2003; BLOOM and ADAMI 2004; FRASER and HIRSH 2004; WALL et al. 2005). In other words, when expression level was statistically controlled, the effects decreased or disappeared. PAL et al. (2003) argued that essential proteins evolve more slowly only because they are highly expressed. To rule out the direct effect of essentiality on evolutionary rate, they argued on the basis of the following two hypothetical relations:

1. Essentiality and transcriptional activity: Each protein molecule may have the same amount of phenotypic contribution to an organism's fitness. Under this hypothesis, proteins that have more phenotypic contribution should have higher levels of active molecules in the cell. However, the validity of this hypothesis is highly questionable as genes involved in functions such as transcriptional regulation, ligand binding, and signal transduction are required only in small quantities even though they are vital for the organism. High abundance does not necessarily mean high fitness effect.

2. Transcriptional activity and selective pressure: Highly expressed genes may prefer translationally efficient codons, which leads to a slow rate of nucleotide sequence changes (AKASHI 2001, 2003; AKASHI and GOJOBORI 2002). Recently, using Saccharomyces as a model organism, DRUMMOND et al. (2005) argued that selection may act on codon preference (for translational accuracy) and on amino acid sequence (for translational robustness) to minimize the detrimental effects of protein misfolding. Since they experience more translation events, highly expressed genes should be subject to stronger selective pressure. …

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