Synthetic genomics is a nascent field of synthetic biology that uses aspects of genetic modification on pre-existing life forms with the intent of producing some product or desired behavior on the part of the life form so created.
Synthetic genomics is unlike genetic modification in the sense that it does not use naturally occurring genes in its life forms. It may make use of custom designed base pair series, though in a more expanded and presently unrealized sense synthetic genomics could utilize genetic codes that are not composed of the two base pairs of DNA that are currently used by life.
The development of synthetic genomics is related to certain recent technical abilities and technologies in the field of genetics. The ability to construct long base pair chains cheaply and accurately on a large scale has allowed researchers to perform experiments on genomes that do not exist in nature. Coupled with the developments in protein folding models and decreasing computational costs the field synthetic genomics is beginning to enter a productive stage of vitality.
The J. Craig Venter Institute has assembled a quasi-synthetic Mycoplasma genitalium bacterial genome by recombination of 25 overlapping fragments in a single step. "The use of yeast recombination greatly simplifies the assembly of large DNA molecules from both synthetic and natural fragments." Other companies, such as Synthetic Genomics, have already been formed to take advantage of the many commercial uses of custom designed genomes.
Unnatural base pair (UBP)
An unnatural base pair (UBP) is a designed subunit (or nucleobase) of DNA which is created in a laboratory and does not occur in nature. In 2012, a group of American scientists led by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in San Diego, California, published that his team designed an unnatural base pair (UBP). The two new artificial nucleotides or Unnatural Base Pair (UBP) were named d5SICS and dNaM. More technically, these artificial nucleotides bearing hydrophobic nucleobases, feature two fused aromatic rings that form a (d5SICS–dNaM) complex or base pair in DNA. In 2014 the same team from the Scripps Research Institute reported that they synthesized a stretch of circular DNA known as a plasmid containing natural T-A and C-G base pairs along with the best-performing UBP Romesberg's laboratory had designed, and inserted it into cells of the common bacterium E. coli that successfully replicated the unnatural base pairs through multiple generations. This is the first known example of a living organism passing along an expanded genetic code to subsequent generations. This was in part achieved by the addition of a supportive algal gene that expresses a nucleotide triphosphate transporter which efficiently imports the triphosphates of both d5SICSTP and dNaMTP into E. coli bacteria. Then, the natural bacterial replication pathways use them to accurately replicate the plasmid containing d5SICS–dNaM.
The successful incorporation of a third base pair is a significant breakthrough toward the goal of greatly expanding the number of amino acids which can be encoded by DNA, from the existing 20 amino acids to a theoretically possible 172, thereby expanding the potential for living organisms to produce novel proteins. The artificial strings of DNA do not encode for anything yet, but scientists speculate they could be designed to manufacture new proteins which could have industrial or pharmaceutical uses.
- Daniel G. Gibson; Gwynedd A. Benders; Kevin C. Axelrod; Jayshree Zaveri; Mikkel A. Algire; Monzia Moodie; Michael G. Montague; J. Craig Venter; Hamilton O. Smith & Clyde A. Hutchison III (2008). "One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome". PNAS 105 (51): 20404–20409. doi:10.1073/pnas.0811011106. PMC 2600582. PMID 19073939.
- Malyshev, Denis A.; Dhami, Kirandeep; Quach, Henry T.; Lavergne, Thomas; Ordoukhanian, Phillip (24 July 2012). "Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet". Proceedings of the National Academy of Sciences of the United States of America (PNAS) 109 (30): 12005–12010. doi:10.1073/pnas.1205176109. Retrieved 2014-05-11.
- Malyshev, Denis A.; Dhami, Kirandeep; Lavergne, Thomas; Chen, Tingjian; Dai, Nan; Foster, Jeremy M.; Corrêa, Ivan R.; Romesberg, Floyd E. (May 7, 2014). "A semi-synthetic organism with an expanded genetic alphabet". Nature (journal). doi:10.1038/nature13314. Retrieved May 7, 2014.
- Callaway, Ewan (May 7, 2014). "Scientists Create First Living Organism With 'Artificial' DNA". Nature News (Huffington Post). Retrieved 8 May 2014.
- Fikes, Bradley J. (May 8, 2014). "Life engineered with expanded genetic code". San Diego Union Tribune. Retrieved 8 May 2014.
- Sample, Ian (May 7, 2014). "First life forms to pass on artificial DNA engineered by US scientists". The Guardian. Retrieved 8 May 2014.
- Pollack, Andrew (May 7, 2014). "Scientists Add Letters to DNA’s Alphabet, Raising Hope and Fear". New York Times. Retrieved 8 May 2014.
- Synthetic Genomes: Technologies and Impact - A 2004 study completed for the DOE on the subject.
- Effects of Developments in Synthetic Genomics: Hearing before the Committee on Energy and Commerce, House of Representatives, One Hundred Eleventh Congress, Second Session, May 27, 2010