Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

Two unpublished letters of Robert Louis Stevenson

This article prints and discusses two uncollected letters by Robert Louis Stevenson to the publishing firm of Chatto & Windus, concerning his book Memories and Portraits.

Cloud base height and cosmic rays

Cosmic rays modify current flow in the global atmospheric electrical circuit. Charging at horizontal layer cloud edges has been observed to be consistent with global circuit vertical current flow through the cloud, which can modify the properties of small and pure water droplets. Studies have been hampered by the absence of cloud edge observations, hence cloud base height information is investigated here. Cloud base height measured at the Lerwick Observatory, Shetland, UK, is analysed using threshold tests and spectral analysis. The cloud base height distributions for low cloud (cloud base less than 800 m) are found to vary with cosmic ray conditions. Further, 27 day and 1.68 year periodicities characteristic of cosmic ray variations are present, weakly, in the cloud base height data of stratiform clouds, when such periodicities are present in neutron monitor cosmic ray data. These features support the idea of propagation of heliospheric variability into layer clouds, through the global atmospheric electric circuit.