Tuesday, September 7, 2010
Bacterial DNA replication is generally extremely accurate; however, spontaneous mutants may have increased fitness due to new beneficial proteins (traits) that may be selected for in a rapidly changing environment. The contribution of post-replication processes to genetic variation has not be examined rigorously and thus transcriptional and translational fidelity (or lack thereof...) has been underappreciated in bacterial selection, and may even be an in-built strategy used by biology to increase protein variation at the single cell level to ensure bacterial robustness under rapid environmental change.
Using a new method for quantifying errors in gene expression at the single cell level in the bacterium Bacillus subtilis, Meyerovich and colleagues reveal that the transcription and translation machinery does not strictly follow the DNA code. The new method relies on the mutation of a chromosomally encoded green fluorescent protein (GFP) reporter allele, containing frameshifts and premature stop codons, so that errors in gene expression result in the formation of GFP, which would then be observable via imaging of single cells in real time. Using this method, the authors show that errors in decoding the DNA sequence occur around 1% of the time. This error rate is at least ten times higher than previous estimates. Furthermore, the frequency of errors increases markedly in response to certain environmental conditions such as nutrient deprivation (stationary phase), lower temperatures, and toxic accumulation. The implications are that many individual protein molecules contain potentially significant variations from the encoded amino acid sequence, and that this could increase survival in fluctuating environments or in response to sudden stress. Consistent with this increased protein plasticity for rapid adaptation, gene-expression errors could combine with a genetic mutation in one gene, allowing the organism to bypass the need to undergo two independent mutations simultaneously. It is unclear whether this error rate increase is due to energetic constraints--the bacteria can't afford error correcting mechanisms under such conditions--or if the bacterial genetic code is selected as a consensus sequence from which protein production generates useful variations.
For any organism, the amount of errors represents a compromise between a cost of dysfunctional proteins and a payoff of beneficial variants that lead to increased phenotypic heterogeneity. It is likely that evolutionary pressure that shapes codon usage would allow different genes to be prone to unequal error rates according to their cellular function.