Artificially Expanded Genetic Information System

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Template:Short description Script error: No such module "Unsubst". Artificially Expanded Genetic Information System (AEGIS) is a synthetic DNA analog experiment that uses some unnatural base pairs from the laboratories of the Foundation for Applied Molecular Evolution in Gainesville, Florida, especially the Steven A. Benner lab. AEGIS is a NASA-funded project to try to understand how extraterrestrial life may have developed.[1] In a 2024 article from the same laboratory, the concept has been broadened into anthropogenic evolvable genetic information systems, still with the same acronym.[2]

Hachimoji DNA is a strict subset of this system and comes from the same laboratory.[3]

Bases

The system uses 12 to 14 different nucleobases in its genetic code, adding four types of base pairs on top of the two natural Watson-Crick base pairs.[1][4][5][6][7]

List of AEGIS base pairs (natural in highlight)
Purine Pyrimidine
Name Abbr. Structure Structure Abbr. Name
Adenine A File:Base pair AT.svg Template:Ubl Thymine
Template:Ubl Template:Ubl File:DiampurineT DNA base pair.svg
Guanine Template:Ubl File:Base pair GC.svg Template:Ubl Cytosine
Isoguanine Template:Ubl File:IG-iC DNA base pair.svg Template:Ubl Isocytosine
File:B-dS aka iG-dS base pair.svg Template:Ubl 1-Methylcytosine
Xanthine Template:Ubl File:XK base pair.svg Template:Ubl 2,4-Diaminopyrimidine
5-Aza-7-deazaguanine Template:Ubl File:PZ base pair.svg Template:Ubl 6-Amino-5-nitropyridin-2-one
4-Aminoimidazo[1,2-a][1,3,5]triazin-2(1H)-one Template:Ubl Template:Ubl 6-Amino-3-nitropyridin-2-ol

Names such as "pyADA", "puDAD" belong to an AGEIS-specific system of denoting nucleobases. PyADA means that the base is a pyrimidine, and from top (5') to down (3') the hydrogen-bonding behavior is acceptor, donor, acceptor. PuDAD means the base is a purine with donor-acceptor-donor pattern. Under this system, all pairs form three hydrogen bonds.[8]

The three-bond system contains considerable flexibility for further modification of nucleosides. Functional groups can be added, removed, or replaced on the non-bonding side of the nucleobase without affecting bonding, much like how uridine (thymine without a methyl group) bonds like thymine in the natural genetic system. The original (1998) formulation only anticipated the possibility of replacing groups on pyAAD (dS), pyADA (T), pyADD (Z), pyDAA (V), and pyDAA (C),[8] but in Benner's 2014 paper all twelve types of bases have one site for group replacement.[9] Benner also indicates in a 2012 report for the DITC that all six purine bases have a second site for attaching another functional group.[10]

Non-canonical bonding

Like natural nucleobases, AEGIS bases can form non-canonical bonds. For example, B can pair with T by tautomerization, Z can pair with G at low pH, and P can pair with C at low pH. A DNA polymerase without access to the unnatural nucleobases would perform these pairings, causing bases to be replaced.[9]

In 2021, it was found that isoguanine (B) can also base-pair with guanine (G) and 5-aza-7-deazaguanine (P) when put in DNA. The purine-purine base pair requires more space than the typical purine-pyrimidine base pair (the natural Watson-Crick A-T C-G pairs and the designed P-Z B-S pairs are all of these type), but the large groove of the DNA double helix provided enough space for this to happen. This "wider" base pair actually enhances the stability of DNA.[11]

Hoogsteen base pairing results in the formating of triplets in nucleic acid tertiary structure.[12]

See also

References

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