Literature

"Another dogma in cell biology seems about to be toppled: If a mutation in a gene doesn't change the basic sequence of building blocks, then it has no effect." This introduces Beckman's news report of some recent research. A silent mutation is a single letter change in a codon that nevertheless produces the same amino acid. According to co-author Kimchi-Sarfaty: "We were all educated that silent mutations should be ignored, and people really don't pay attention to them." However, this entered education because of the dominance of theory rather than the strength of evidence. The new paper provides enough data to show that many areas of molecular biology need to be revisited. "This may be a generalizable phenomenon that may lead to changes in function we haven't been thinking about" said co-author Gottesman.
The authors draw attention to possible medical implications, "raising the possibility that mutations that do not change coding sequence may contribute to disease by a similar mechanism". But the findings are also relevant to genome similarity measures (particularly humans and chimps) and also the detection of signatures of natural selection in genome sequences (based on the neutral theory of molecular evolution). They allow us to anticipate some revisions to previously reported findings.
Perhaps the most interesting comment comes from Pearson: "Biologists have realized that the genetic code harbours a layer of information that they have largely ignored. Again." This needs to be digested. Why has this layer of information been ignored? Why did it become a "dogma in cell biology"? The answer seems to be that the mindset of molecular biologists is to assume simplicity rather than complexity in the genetic code. This mindset is driven by the thought that cellular information is ultimately mindless and a product of natural forces. This new research allows us once again to ask whether it is time to assume complexity rather than simplicity because design inferences allow us to recognise intelligent agency in the genetic code.

A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, Michael M. Gottesman.
Science Online December 21, 2006, DOI: 10.1126/science.1135308

Abstract: Synonymous Single Nucleotide Polymorphisms (SNPs) do not change the coding sequences, and, therefore, are not expected to change the function of the protein in which they occur. Here, we report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of the MDR1 gene product, P-glycoprotein (P-gp), nonetheless results in P-gp with altered drug and inhibitor interactions. Similar mRNA levels and protein, but altered conformations were found for wild-type and polymorphic P-gp. We hypothesize that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of co-translational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.

See also:

Choi, C.Q. "Silent" mutations are not always silent, The Scientist, 21st December 2006.
http://www.the-scientist.com/news/home/38329/

Pearson, H. Silent mutations speak up, news@nature.com: 21 December 2006; | doi:10.1038/
http://www.nature.com/news/2006/061218/full/061218-12.html

Beckman, M. The Sound of a Silent Mutation, ScienceNOW Daily News, 22 December 2006
http://sciencenow.sciencemag.org/cgi/content/full/2006/1222/2

Amato, I. Silent No Longer, Chemical & Engineering News, January 22, 2007, Volume 85, Number 04, pp. 38-40.

"The more scientists study the genetic code, the more it reads like poetry. In a poem, every word, every line break, even every syllable can carry more than a literal meaning. So too can the molecular letters, syllables, and words of the genetic code carry more biologically relevant meanings than they appear to at first.
Now, a cadre of researchers is discovering intriguing depths of meaning in "synonyms" in the genetic code - very short wordlike sequences, or codons, that translate into exactly the same amino acids during the construction of a protein. Scientists are finding that synonymous codons influence the temporal pattern by which a messenger RNA (mRNA) molecule bearing genetic specifications from a cell's nucleus is translated by machinelike ribosomes into protein molecules." [snip]