Hachimoji DNA and RNA: A genetic system with eight building blocks
Abstract
We report DNA- and RNA-like systems built from eight nucleotide “letters” (hence the name “hachimoji”) that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to increase the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos.
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1547949
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Published Article
- Journal Name:
- Science
- Additional Journal Information:
- Journal Name: Science Journal Volume: 363 Journal Issue: 6429; Journal ID: ISSN 0036-8075
- Publisher:
- American Association for the Advancement of Science (AAAS)
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Hoshika, Shuichi, Leal, Nicole A., Kim, Myong-Jung, Kim, Myong-Sang, Karalkar, Nilesh B., Kim, Hyo-Joong, Bates, Alison M., Watkins, Jr., Norman E., SantaLucia, Holly A., Meyer, Adam J., DasGupta, Saurja, Piccirilli, Joseph A., Ellington, Andrew D., SantaLucia, Jr., John, Georgiadis, Millie M., and Benner, Steven A. Hachimoji DNA and RNA: A genetic system with eight building blocks. United States: N. p., 2019.
Web. doi:10.1126/science.aat0971.
Hoshika, Shuichi, Leal, Nicole A., Kim, Myong-Jung, Kim, Myong-Sang, Karalkar, Nilesh B., Kim, Hyo-Joong, Bates, Alison M., Watkins, Jr., Norman E., SantaLucia, Holly A., Meyer, Adam J., DasGupta, Saurja, Piccirilli, Joseph A., Ellington, Andrew D., SantaLucia, Jr., John, Georgiadis, Millie M., & Benner, Steven A. Hachimoji DNA and RNA: A genetic system with eight building blocks. United States. https://doi.org/10.1126/science.aat0971
Hoshika, Shuichi, Leal, Nicole A., Kim, Myong-Jung, Kim, Myong-Sang, Karalkar, Nilesh B., Kim, Hyo-Joong, Bates, Alison M., Watkins, Jr., Norman E., SantaLucia, Holly A., Meyer, Adam J., DasGupta, Saurja, Piccirilli, Joseph A., Ellington, Andrew D., SantaLucia, Jr., John, Georgiadis, Millie M., and Benner, Steven A. Thu .
"Hachimoji DNA and RNA: A genetic system with eight building blocks". United States. https://doi.org/10.1126/science.aat0971.
@article{osti_1547949,
title = {Hachimoji DNA and RNA: A genetic system with eight building blocks},
author = {Hoshika, Shuichi and Leal, Nicole A. and Kim, Myong-Jung and Kim, Myong-Sang and Karalkar, Nilesh B. and Kim, Hyo-Joong and Bates, Alison M. and Watkins, Jr., Norman E. and SantaLucia, Holly A. and Meyer, Adam J. and DasGupta, Saurja and Piccirilli, Joseph A. and Ellington, Andrew D. and SantaLucia, Jr., John and Georgiadis, Millie M. and Benner, Steven A.},
abstractNote = {We report DNA- and RNA-like systems built from eight nucleotide “letters” (hence the name “hachimoji”) that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to increase the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos.},
doi = {10.1126/science.aat0971},
journal = {Science},
number = 6429,
volume = 363,
place = {United States},
year = {2019},
month = {2}
}
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Works referenced in this record:
Evolution of Functional Six-Nucleotide DNA
journal, May 2015
- Zhang, Liqin; Yang, Zunyi; Sefah, Kwame
- Journal of the American Chemical Society, Vol. 137, Issue 21
Enzymic recognition of the base pair between isocytidine and isoguanosine
journal, October 1993
- Switzer, Christopher Y.; Moroney, Simon E.; Benner, Steven A.
- Biochemistry, Vol. 32, Issue 39
KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick geometry
journal, June 2012
- Betz, Karin; Malyshev, Denis A.; Lavergne, Thomas
- Nature Chemical Biology, Vol. 8, Issue 7
Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern
journal, October 2006
- Yang, Zunyi; Hutter, Daniel; Sheng, Pinpin
- Nucleic Acids Research, Vol. 34, Issue 21
Cloning, expression, and purification of a catalytic fragment of moloney murine leukemia virus reverse transcriptase: Crystallization of nucleic acid complexes
journal, July 1998
- Sun, Dunming; Jessen, Sven; Liu, Chunhui
- Protein Science, Vol. 7, Issue 7
Snapshots of an evolved DNA polymerase pre- and post-incorporation of an unnatural nucleotide
journal, July 2018
- Singh, Isha; Laos, Roberto; Hoshika, Shuichi
- Nucleic Acids Research, Vol. 46, Issue 15
Thermodynamics and NMR of Internal G·T Mismatches in DNA
journal, August 1997
- Allawi, Hatim T.; SantaLucia, John
- Biochemistry, Vol. 36, Issue 34
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997
- Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures
journal, September 2003
- Lu, X. -J.
- Nucleic Acids Research, Vol. 31, Issue 17
An unnatural base pair for incorporating amino acid analogs into proteins
journal, February 2002
- Hirao, Ichiro; Ohtsuki, Takashi; Fujiwara, Tsuyoshi
- Nature Biotechnology, Vol. 20, Issue 2
Crystal structures of oligonucleotides including the integrase processing site of the Moloney murine leukemia virus
journal, November 2006
- Montaño, Sherwin P.; Coté, Marie L.; Roth, Monica J.
- Nucleic Acids Research, Vol. 34, Issue 19
Generation of high-affinity DNA aptamers using an expanded genetic alphabet
journal, April 2013
- Kimoto, Michiko; Yamashige, Rie; Matsunaga, Ken-ichiro
- Nature Biotechnology, Vol. 31, Issue 5
Ribonucleosides for an Artificially Expanded Genetic Information System
journal, March 2014
- Kim, Hyo-Joong; Leal, Nicole A.; Hoshika, Shuichi
- The Journal of Organic Chemistry, Vol. 79, Issue 7
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
A semi-synthetic organism that stores and retrieves increased genetic information
journal, November 2017
- Zhang, Yorke; Ptacin, Jerod L.; Fischer, Emil C.
- Nature, Vol. 551, Issue 7682
Use of an N-terminal fragment from Moloney murine leukemia virus reverse transcriptase to facilitate crystallization and analysis of a pseudo-16-mer DNA molecule containing G–A mispairs
journal, September 2000
- Coté, Marie L.; Yohannan, Sarah J.; Georgiadis, Millie M.
- Acta Crystallographica Section D Biological Crystallography, Vol. 56, Issue 9
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
A G-quadruplex–containing RNA activates fluorescence in a GFP-like fluorophore
journal, June 2014
- Huang, Hao; Suslov, Nikolai B.; Li, Nan-Sheng
- Nature Chemical Biology, Vol. 10, Issue 8
2′-Deoxy-1-methylpseudocytidine, a stable analog of 2′-deoxy-5-methylisocytidine
journal, May 2009
- Kim, Hyo-Joong; Leal, Nicole A.; Benner, Steven A.
- Bioorganic & Medicinal Chemistry, Vol. 17, Issue 10
Difluorotoluene, a Nonpolar Isostere for Thymine, Codes Specifically and Efficiently for Adenine in DNA Replication
journal, February 1997
- Moran, Sean; Ren, Rex X. -F.
- Journal of the American Chemical Society, Vol. 119, Issue 8
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
journal, April 1953
- Watson, J. D.; Crick, F. H. C.
- Nature, Vol. 171, Issue 4356
Amplification, Mutation, and Sequencing of a Six-Letter Synthetic Genetic System
journal, September 2011
- Yang, Zunyi; Chen, Fei; Alvarado, J. Brian
- Journal of the American Chemical Society, Vol. 133, Issue 38
Ribosome-mediated incorporation of a non-standard amino acid into a peptide through expansion of the genetic code
journal, April 1992
- Bain, J. D.; Switzer, Christopher; Chamberlin, Richard
- Nature, Vol. 356, Issue 6369, p. 537-539
Spinach RNA aptamer detects lead( ii ) with high selectivity
journal, January 2015
- DasGupta, Saurja; Shelke, Sandip A.; Li, Nan-sheng
- Chemical Communications, Vol. 51, Issue 43
Enzymatic incorporation of a third nucleobase pair
journal, June 2007
- Yang, Z.; Sismour, A. M.; Sheng, P.
- Nucleic Acids Research, Vol. 35, Issue 13
A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics
journal, February 1998
- SantaLucia, J.
- Proceedings of the National Academy of Sciences, Vol. 95, Issue 4
Model bias in macromolecular crystal structures
journal, November 1992
- Hodel, A.; Kim, S. H.; Brünger, A. T.
- Acta Crystallographica Section A Foundations of Crystallography, Vol. 48, Issue 6
PCR amplification of DNA containing non-standard base pairs by variants of reverse transcriptase from Human Immunodeficiency Virus-1
journal, January 2004
- Sismour, A. M.
- Nucleic Acids Research, Vol. 32, Issue 2
Alternative Watson–Crick Synthetic Genetic Systems
journal, September 2016
- Benner, Steven A.; Karalkar, Nilesh B.; Hoshika, Shuichi
- Cold Spring Harbor Perspectives in Biology, Vol. 8, Issue 11
Transcription yield of fully 2′-modified RNA can be increased by the addition of thermostabilizing mutations to T7 RNA polymerase mutants
journal, July 2015
- Meyer, Adam J.; Garry, Daniel J.; Hall, Bradley
- Nucleic Acids Research, Vol. 43, Issue 15
Transcription, Reverse Transcription, and Analysis of RNA Containing Artificial Genetic Components
journal, July 2014
- Leal, Nicole A.; Kim, Hyo-Joong; Hoshika, Shuichi
- ACS Synthetic Biology, Vol. 4, Issue 4
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
RNA Mimics of Green Fluorescent Protein
journal, July 2011
- Paige, J. S.; Wu, K. Y.; Jaffrey, S. R.
- Science, Vol. 333, Issue 6042
Investigation of the Structural Basis for Thermodynamic Stabilities of Tandem GU Mismatches: Solution Structure of (rGAG GU CUC) 2 by Two-Dimensional NMR and Simulated Annealing † , ‡
journal, January 1996
- McDowell, Jeffrey A.; Turner, Douglas H.
- Biochemistry, Vol. 35, Issue 45
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
On the wagon—DNA polymerase joins "H-bonds anonymous"
journal, July 1999
- Goodman, Myron F.
- Nature Biotechnology, Vol. 17, Issue 7