Artificially Expanded Genetic Information System

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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

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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
  • T
  • pyADA
 Thymine
  • AminoA
  • DAP
  • puDAD
Guanine
  • G
  • puADD
  • C
  • pyDAA
 Cytosine
Isoguanine
  • iG
  • B
  • puDDA
  • iC
  • rS
  • pyAAD
 Isocytosine
  • dS
  • pyAAD
 1-Methylcytosine
Xanthine
  • X
  • puADA
  • K
  • pyDAD
 2,4-Diaminopyrimidine
5-Aza-7-deazaguanine
  • P
  • puAAD
  • Z
  • pyDDA
 6-Amino-5-nitropyridin-2-one
4-Aminoimidazo[1,2-a][1,3,5]triazin-2(1H)-one
  • J
  • puDAA
  • V
  • PyADD
 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

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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

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References

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  1. ^ a b Lloyd, Robin (February 14, 2009). "New Artificial DNA Points to Alien Life". LiveScience. Retrieved 5 July 2016.
  2. ^ Wang, B; Kim, HJ; Bradley, KM; Chen, C; McLendon, C; Yang, Z; Benner, SA (25 December 2024). "Joining Natural and Synthetic DNA Using Biversal Nucleotides: Efficient Sequencing of Six-Nucleotide DNA". Journal of the American Chemical Society. 146 (51): 35129–35138. doi:10.1021/jacs.4c11043. PMID 39625448.
  3. ^ Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins NE, SantaLucia HA, Meyer AJ, DasGupta S, Ellington AD, SantaLucia J, Georgiadis MM, Benner SA (February 2019). "Hachimoji DNA and RNA: A genetic system with eight building blocks". Science. 363 (6429): 884–887. Bibcode:2019Sci...363..884H. doi:10.1126/science.aat0971. PMC 6413494. PMID 30792304.
  4. ^ Yang, Z.; Hutter, D.; Sheng, P.; Sismour, A. M.; Benner, S. A. (29 October 2006). "Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern". Nucleic Acids Research. 34 (21): 6095–6101. doi:10.1093/nar/gkl633. PMC 1635279. PMID 17074747.
  5. ^ Benner, SA; Hutter, D; Sismour, AM (1 September 2003). "Synthetic biology with artificially expanded genetic information systems. From personalized medicine to extraterrestrial life". Nucleic Acids Research. Supplement. 3 (3): 125–6. doi:10.1093/nass/3.1.125. PMID 14510412.
  6. ^ Benner, Steven A. (December 2010). "Defining Life". Astrobiology. 10 (10): 1021–1030. Bibcode:2010AsBio..10.1021B. doi:10.1089/ast.2010.0524. PMC 3005285. PMID 21162682.
  7. ^ Klotz, Irene (February 27, 2009). "Synthetic life form grows in Florida lab". Science. Archived from the original on January 13, 2016. Retrieved 5 July 2016.
  8. ^ a b Benner, SA; Battersby, TR; Eschgfaller, B; Hutter, D; Kodra, JT; Lutz, S; Arslan, T; Baschlin, DK; Blattler, M; Egli, M; Hammer, C; Held, HA; Horlacher, J; Huang, Z; Hyrup, B; Jenny, TF; Jurczyk, SC; Konig, M; von Krosigk, U; Lutz, MJ; MacPherson, LJ; Moroney, SE; Muller, E; Nambiar, KP; Piccirilli, JA; Switzer, CY; Vogel, JJ; Richert, C; Roughton, AL; Schmidt, J; Schneider, KC; Stackhouse, J (February 1998). "Redesigning nucleic acids". Pure and applied chemistry. Chimie pure et appliquee. 70 (2): 263–6. doi:10.1351/pac199870020263. PMID 11542721.
  9. ^ a b Bradley, K. M.; Benner, S. A. (2014). "OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands". Beilstein Journal of Organic Chemistry. 10: 1826–1833. doi:10.3762/bjoc.10.192. PMC 4142867. PMID 25161743.
  10. ^ Benner, Steve A (August 5, 2012). "Design Automation Software for DNA-based Nano-Sensor Architecture" (PDF). apps.dtic.mil.
  11. ^ Zhang, A; Kondhare, D; Leonard, P; Seela, F (6 May 2021). "5-Aza-7-deazaguanine-Isoguanine and Guanine-Isoguanine Base Pairs in Watson-Crick DNA: The Impact of Purine Tracts, Clickable Dendritic Side Chains, and Pyrene Adducts". Chemistry (Weinheim an der Bergstrasse, Germany). 27 (26): 7453–7466. doi:10.1002/chem.202005199. PMC 8251886. PMID 33443814.
  12. ^ Jena, N. R.; Shukla, P. K. (2023). "Structure and stability of different triplets involving artificial nucleobases: clues for the formation of semisynthetic triple helical DNA". Scientific Reports. 13: 19246. Bibcode:2023NatSR..1319246J. doi:10.1038/s41598-023-46572-4. PMC 10630353.


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