Genetic alphabet

Piccirilli, J. A., et al. (1990). Enzymatic incorporation of a new base pair into DNA and RNA extends the genetic alphabet. Nature 343,33-37. 

Incorporation of nonnatural polyfluorinated bases, capable of enhanced (or hyper ) hydrophobic interactions, thus expands the genetic alphabet beyond the natural one used in replication. It illustrates the emerging role of F-com-pounds in developing chemistry, including constitutional dynamic biochemistry, that lies well beyond nature. 

Figure 3.5 Above are the five nucleotides that make up nucleic acids. Like a genetic alphabet, a nucleotide s order determines the structure of specific proteins.

The synthetic genetic system has even been coupled to unnatural protein synthesis. Adding extra letters to the genetic alphabet has been shown to increase the number of triplet codons that are accessible to a messenger RNA. In 1993, Bain et al. showed that additional triplet codons made possible by extra nucleobases and delivered by synthetic biological efforts could encode extra amino acids.14 That result was obtained with the terran ribosome. 

Novel bases for the genetic alphabet have been synthesised and evaluated... 

Suggested by E. Szathmdry. Four letters in the genetic alphabet a frozen evolutionary optimum Proceedings of the Royal Society, B245 (1991), 91-9. 

E. Szathmaiy. Why are there four letters in the genetic alphabet Nature Reviews Genetics, 4 (2003), 995-1001. See also P. P. Gardner, B. R. Holland, V. Moulton,... 

Y. Wu et al. Efforts toward expansion of the genetic alphabet optimization of interbase hydrophobic interactions. Journal of the American Chemical Society, 122 (2000), 7621-32. 

Sherrill CB, et al. (2004). Nucleic acid analysis using an expanded genetic alphabet to quench fluorescence. J. Am. Chem. Soc., 126 4550-4556. 

Hirao I, Kimoto M (2012) Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma. Proc Jpn Acad Ser B Phys Biol Sci 88(7) 345-367 Yamashige R, Kimoto M, Takezawa Y, Sato A, Mitsui T, Yokoyama S, Hirao I (2012) Highly specific unnatural base pair systems as a third base pair for PCR amplification. Nucleic Acids Res 40(6) 2793-2806. doi 10.1093/nar/gkrl068... 

Li L, Degardin M, Lavergne T, Malyshev DA, Dhami K, Ordoukhanian P, Romesberg FE (2014) Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications. J Am Chem Soc 136(3) 826-829. doi 10.1021/ja408814g... 

Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Correa IR Jr, Romesberg FE (2014) A semi-synthetic organism with an expanded genetic alphabet. Nature 509(7500) 385-388. doi 10.1038/naturel3314... 

Dhami K, Malyshev DA, Ordoukhanian P, KubelkaT, HocekM, Romesbeig FE (2014) Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet. Nucleic Acids Res 42(16) 10235-10244. doi 10.1093/nar/gku715... 

Malyshev DA, Dhami K, Quach HT, Lavergne T, Ordoukhanian P, Torkamani A, Romesberg FE (2012) Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet. Proc Natl Acad Sci USA 109(30) 12005 12010. doi 10.1073/pnas.l205176109... 

Kimoto M, Mitsui T, Yokoyattta S, Hirao I (2010) A unique fluorescent base analogue for the expansion of the genetic alphabet. J Am Chem Soc 132(14) 4988 989. doi 10.1021/ja100806c... 

Someya T, Ando A, Kimoto M, Hirao I (2015) Site-specific labeling of RNA by combining genetic alphabet expansion transcription and copper-fiee click chemistry. Nucleic Acids Res. doi 10.1093/ nar/gkv638... 

Kimoto M, Yamashige R, Matsunaga K, Yokoyama S, Flirao I (2013) Generation of high-affinity DNA aptamers using an expanded genetic alphabet. Nat Biotechnol 31(5) 453-457. doi 10.1038/ nbt.2556... 

Watson-Crick hydrogen bonding in natural base pairs is essential for most of the DNA functions. Initial effort was made largely to expand the genetic alphabet using altered hydrogen bonding. Benner and coworkers pioneered a way to enzymatic... 

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