Wednesday, April 1, 2009

Freedom of expression: gene expression that is

By Kristopher Hite

Life is written in a language of chemical sentences. In 2006 a group of researchers began the process of engineering new letters to be incorporated into the genetic alphabet. The naturally occurring genetic alphabet is made up of 20 chemical letters (amino acids). These letters are arranged in the correct order by molecular machines, called ribosomes, into words that make sense (proteins). There are words of all sizes that perform key functions in all organisms, from two letter hormones to the epic 26,000 lettered titan titin muscle protein.

Each of the 20 naturally occurring amino acids is known by the translating machinery to correspond to a sequence of three specific nucleotide bases (codon). Because there are four nucleotide bases and they come together in groups of three (4x4x4 = 64) there are 64 different combinations of these base pairs. Because there are only 20 naturally occurring amino acids and 64 ways to code for them that leaves 44 options left open to code for other things.

Nature uses most of these extra codons as redundant codes for the same amino acid so some letters will have 2-6 different codes all calling for the same letter. But there are some of these extra codons that are nonsensical and do nothing apparently useful. What this research group did was take advantage of these extra three letter codons and engineered a special translator molecule known as transfer RNA or tRNA that they attached to new unnatural letters - (man made amino acids).

The mind blowing novelty of this expanded genetic alphabet is only now being realized for practical purposes. With new man-made letters within nature's alphabet of life researchers are taking this patented technology and using it to create Frankenstein proteins with diverse and useful features like hemoglobin mimicry and in-cell localization. This process will be at the heart of synthetic biology.

The question stands... Is a patent for an unnatural letter allowed? Apparently it is, according to the US government's patent office. But does that mean that I could invent new letters for the English alphabet and patent them to make a profit if others eventually use them? How do you think the ethics surrounding this technology will be considered when the future of human gene patents is decided?

Xie, J., & Schultz, P. (2006). A chemical toolkit for proteins — an expanded genetic code Nature Reviews Molecular Cell Biology, 7 (10), 775-782 DOI: 10.1038/nrm2005

Note: I have posted these thoughts before but I thought the topic relevant to current discussions stemming from last weeks issue of Nature. Also, TPG has experienced a large increase in its viewing audience since last I mused on this topic.

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