Hachimoji DNA

Hachimoji DNA (from Japanese 八文字 hachimoji, "eight letters") is a synthetic nucleic acid analog that uses four synthetic nucleotides in addition to the four present in the natural nucleic acids, DNA and RNA. This leads to four allowed base pairs: two unnatural base pairs formed by the synthetic nucleobases in addition to the two normal pairs. Hachimoji bases have been demonstrated in both DNA and RNA analogs, using deoxyribose and ribose respectively as the backbone sugar.[1][2][3][4][5]

Further information: Xenobiology
A double helix of natural DNA. Hachimoji DNA adopts a similar structure.

Benefits of such a nucleic acid system may include an enhanced ability to store data, as well as insights into what may be possible in the search for extraterrestrial life.[5][6]

The hachimoji DNA system produced one type of catalytic RNA (ribozyme or aptamer) in vitro.

Description

Natural DNA is a molecule carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life. DNA is a polynucleotide as it is composed of simpler monomeric units called nucleotides; when double-stranded, the two chains coil around each other to form a double helix.[7][8]

In natural DNA, each nucleotide is composed of one of four nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound to each other with hydrogen bonds, according to base pairing rules (A with T and C with G), to make double-stranded DNA.

Hachimoji DNA is similar to natural DNA but differs in the number, and type, of nucleobases.[1][5] Unnatural nucleobases, more hydrophobic than natural bases,[9][10] are used in successful hachimoji DNA. Such a DNA always formed the standard double helix, no matter what sequence of bases were used. An enzyme (T7 polymerase) was adapted by the researchers to be used in vitro to transcribe hachimoji DNA into hachimoji RNA, which, in turn, produced chemical activity in the form of a glowing green fluorophore.[4][5]

New base pairs

DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hachimoji DNA uses an additional four synthetic nucleotides to form four types of base pairs, two of which are unnatural: P binds with Z and B binds with S (dS in DNA, rS in RNA).[1]

BaseNameFormulaSMILESStructureChemSpiderPubChem
P 2-Aminoimidazo[1,2a][1,3,5]triazin-4(1H)-one

2-amino-8-(1′-b-D-2′-deoxyribofuranosyl)-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one[1]

 C5H5N5O C1=CN2C(=O)NC(=NC2=N1)N
10205066 135600909
Z 6-Amino-5-nitropyridin-2-one

6-amino-3-(1′-b-D-2′-deoxyribofuranosyl)-5-nitro-1H-pyridin-2-one[1]

 C5H5N3O3 C1=CC(=O)NC(=C1[N+](=O)[O-])N
9357814 11182729
B Isoguanine

6-amino-9[(1′-b-D-2′-deoxyribofuranosyl)-4-hydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1H-purin-2-one[1]

 C5H5N5O C1=NC2=NC(=O)NC(=C2N1)N
69351 76900
S rS Isocytosine C4H5N3O C1=CN=C(NC1=O)N
60309 66950
dS 1-Methylcytosine

3-methyl-6-amino-5-(1′-b-D-2′-deoxyribofuranosyl)-pyrimidin-2-one[1]

 C5H7N3O CN1C=CC(=NC1=O)N
71474 79143
Base pairings in hachimoji DNA (left, dR = deoxyribose) and hachimoji RNA (right, R = ribose).[1]
The natural bases are in the upper row; the unnatural, synthetic bases are in the lower row.
Hydrogen bonds are dashed green lines, with acceptor atoms in red.

Background

Earlier, the research group responsible for the hachimoji DNA system, headed by Harvard University chemist Steven Benner, had studied a synthetic DNA analog system, named Artificially Expanded Genetic Information System (AEGIS), that used twelve different nucleotides, including the four found in DNA.[11][12][13][14][15]

Biology

Scripps Research chemist Floyd Romesberg, noted for creating the first Unnatural Base Pair (UBP), and expanding the genetic alphabet of four letters to six in 2012,[16] stated that the invention of the hachimoji DNA system is an example of the fact that the natural bases (G, C, A and T) "are not unique".[17][18] Creating new life forms may be possible, at least theoretically,[9] with the new DNA system.[18] For now, however, the hachimoji DNA system is not self-sustaining; the system needs a steady supply of unique building blocks and proteins found only in the laboratory. As a result, "Hachimoji DNA can go nowhere if it escapes the laboratory."[4]

Applications

NASA funded this research to "expand[s] the scope of the structures that we might encounter as we search for life in the cosmos".[1] According to Lori Glaze of the Planetary Science Division of NASA, "Life detection is an increasingly important goal of NASA's planetary science missions, and this new work [with hachimoji DNA] will help us to develop effective instruments and experiments that will expand the scope of what we look for."[3][19] Research team leader Steven Benner notes, "By carefully analyzing the roles of shape, size and structure in hachimoji DNA, this work expands our understanding of the types of molecules that might store information in extraterrestrial life on alien worlds."[20]

According to researchers,[1] hachimoji DNA could also be used "to develop clean diagnostics for human diseases, in DNA digital data storage, DNA barcoding, self-assembling nanostructures, and to make proteins with unusual amino acids. Parts of this hachimoji DNA are already being commercially produced by Firebird Biomolecular Sciences LLC".[1][4]

See also

References
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  2. American Association for the Advancement of Science (21 February 2019). "Hachimoji – Expanding the genetic alphabet from four to eight". EurekAlert!. Retrieved 22 February 2019.
  3. Brown D, Landau E (21 February 2019). "Research creates DNA-like molecule to aid search for alien life". Phys.org. Retrieved 22 February 2019.
  4. Dumé B (22 February 2019). "Hachimoji DNA doubles the genetic code". Physics World. Retrieved 22 February 2019.
  5. Zimmer C (21 February 2019). "DNA Gets a New — and Bigger — Genetic Alphabet - DNA is spelled out with four letters, or bases. Researchers have now built a system with eight. It may hold clues to the potential for life elsewhere in the universe and could also expand our capacity to store digital data on Earth". The New York Times. Retrieved 21 February 2019.
  6. Dvorsky G (22 February 2019). "Freaky Eight-Letter DNA Could Be the Stuff Aliens Are Made Of". Gizmodo. Retrieved 23 February 2019.
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  8. Purcell A. "DNA". Basic Biology. Archived from the original on 5 January 2017. Retrieved 21 February 2019.
  9. Warren M (February 2019). "Four new DNA letters double life's alphabet". Nature. 566 (7745): 436. Bibcode:2019Natur.566..436W. doi:10.1038/d41586-019-00650-8. PMID 30809059.
  10. Thulin L (25 February 2019). "Scientists Successfully Double the DNA Alphabet - "Hachimoji DNA" is structurally sound, offers new possibilities for data storage and raises questions about the molecular makeup potential alien life". Smithsonian Magazine. Retrieved 25 February 2019.
  11. Yang Z, Hutter D, Sheng P, Sismour AM, Benner SA (29 October 2006). "Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern". Nucleic Acids Research. 34 (21): 6095–101. doi:10.1093/nar/gkl633. PMC 1635279. PMID 17074747.
  12. 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.
  13. Benner SA (December 2010). "Defining life". Astrobiology. 10 (10): 1021–30. Bibcode:2010AsBio..10.1021B. doi:10.1089/ast.2010.0524. PMC 3005285. PMID 21162682.
  14. Klotz I (27 February 2009). "Synthetic life form grows in Florida lab". Science. Retrieved 27 February 2019.
  15. Lloyd R (14 February 2009). "New Artificial DNA Points to Alien Life". LiveScience. Retrieved 27 February 2019.
  16. Malyshev DA, Dhami K, Quach HT, Lavergne T, Ordoukhanian P, Torkamani A, Romesberg FE (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. 109 (30): 12005–10. Bibcode:2012PNAS..10912005M. doi:10.1073/pnas.1205176109. PMC 3409741. PMID 22773812.
  17. Saplakoglu Y (21 February 2019). "Scientists Have Created Synthetic DNA with 4 Extra Letters". Live Science. Retrieved 22 February 2019.
  18. Molteni M (21 February 2019). "Doubling Our DNA Building Blocks Could Lead To New Life Forms". Wired. Retrieved 22 February 2019.
  19. Stickland A (21 February 2019). "Synthetic DNA could help with search for alien life". CNN News. Retrieved 22 February 2019.
  20. Carpineti A (22 February 2019). "New Artificial DNA Has Doubled The Alphabet Of Life". IFLScience.com. Retrieved 22 February 2019.

Further reading
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