Genome-wide measurements of mRNA stability in E. coli and S. cerevisiae have found that highly expressed mRNAs are on average no more stable than weakly expressed mRNAs (Bernstein et al 2002; Wang et al 2002). This is surprising, both because stabilizing an mRNA directly increases its levels, and because it seems inefficient for the cell to turn over highly expressed mRNAs rapidly. These results also imply that natural selection is operating on mRNA levels and/or half-lives, independent of selection on protein levels, and suggest that we should analyze the selection pressure on mRNA metabolism.
Using an optimal growth rate assumption (Ehrenburg and Kurland 1984), I've derived a relationship between rates of mRNA and protein turnover and increases in fitness by reducing the time to adapt to changing conditions or by reducing stochastic fluctuations in protein levels. The benefits are balanced by the costs of increased turnover in energy expenditure and in increased mass investment in RNA polymerase and/or ribosomes. Whether using power-law assumptions from metabolic control analysis (Fell 1992) or a linear model as in flux balance analysis (Schilling et al 2000), the model suggests that mRNAs should turn over two orders of magnitude faster than proteins, which is correct, and that more highly expressed mRNAs should turn over more slowly, which does not fit the data. However, if we consider that adaptation to changing conditions requires that groups of genes with disparate expression levels turn on simulatenously, then the optimal mRNA turnover rates become independent of expression levels. This explanation also suggests that the cost of stochastic fluctuations is not a significant factor in determining the optimal turnover rates.
For more information, see my position paper.
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