Previously on ENV, I have described several remarkable features — and the finely tuned characteristics — of the genetic code found in nature. A new study, published in the journal Nature and conducted by a research team at the University of California, San Francisco, identifies an additional, hitherto uncovered, layer of information associated with the genetic code.
Focusing on the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Escherichia coli, the researchers used a technique called ribosome profiling (a method for determining the position of a ribosome bound to mRNA) to draw conclusions about the rate of protein synthesis.
The conventional genetic code involves 20 different amino acids, which map to 64 different triplets of nucleotides called codons. Since there are many more codons than amino acids, this means that there is an element of redundancy because amino acids can be specified by multiple codons. As I noted before, this redundancy allows the genetic code to be exquisitely fine-tuned to minimize error.
The paper explains that “redundancy in the genetic code allows the same protein to be translated at different rates.” In other words, even so-called silent substitutions (that is, those mutations that exchange a nucleotide for another without changing the amino acid specified by the codon) can have an impact on the rate of translation of the protein product.
The researchers found that genes containing a particular class of sequences that are involved in ribosome-binding — known as Shine-Dalgarno sequences — translated into their protein product at a slower rate than genes containing different codons specifying the same amino acids. They further demonstrated that translational pauses can, in fact, be produced by introducing these Shine-Dalgarno sequences into genes.
The authors report:
Shine-Dalgarno-(SD)-like features within coding sequences cause pervasive translational pausing. Using an orthogonal ribosome possessing an altered anti-SD sequence, we show that pausing is due to hybridization between the mRNA and 16S ribosomal RNA of the translating ribosome. In protein-coding sequences, internal SD sequences are disfavoured, which leads to biased usage, avoiding codons and codon pairs that resemble canonical SD sites. Our results indicate that internal SD-like sequences are a major determinant of translation rates and a global driving force for the coding of bacterial genomes. [internal citations omitted]
What could be the functional significance of such a mechanism for ribosome pausing? The authors observe:
The observation that the ability of elongating ribosomes to interact with SD-like sequences is highly conserved suggests that this mechanism of pausing is exploited for functional purposes. Indeed, a highly conserved internal SD site exists in the gene encoding peptide chain release factor 2 (RF2). This sequence has an important function in promoting a translational frameshift to enable its expression. In addition, pausing at internal SD-like sites could modulate the co-translational folding of the nascent peptide chain. Finally, given the coupling between transcription and translation in bacteria, pausing at SD sites could be exploited for transcriptional regulation. We observed internal SD sites and pausing near the stop codon of transcription attenuation leader peptides, including trpL and thrL. In contrast to ribosome stalling at regulatory codons during starvation, slow translation near the stop codon could protect alternative structural mRNA elements to prevent the formation of anti-termination stem-loops, thereby ensuring proper transcription termination. Our approach and the genome-wide data lay the groundwork for further gene-specific functional studies of translational pausing.
The observation that silent synonymous base-pair substitutions can be of functional relevance to gene expression may undercut an argument made often in support of common descent — that is, the argument that, in genes shared between different taxa, a higher frequency of shared synonymous (assumed to be functionally insignificant) substitutions, than would be predicted under the assumption of neutral evolution, necessarily implies common ancestry.
As our knowledge and understanding of the elegant machinery, mechanisms, and information-processing systems present in living systems grows deeper, the more we are filled with a tremendous sense of awe at the sheer marvel of engineering that is life.
Such a remarkable, multi-dimensional coding system assuredly could only have arisen by means of intelligent programming and design. As we learn more about the remarkable information systems intrinsic to life in years to come, the genuine design in these systems will doubtless become even more apparent.