Hachimoji DNA New Base Pairs
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Hachimoji DNA (from Japanese ''hachimoji'', "eight letters") is a synthetic nucleic acid analog that uses four synthetic nucleotides in addition to the four present in the natural
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
s, DNA and RNA. This leads to four allowed
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s: 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. 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 Extraterrestrial life, colloquially referred to as alien life, is life that may occur outside Earth and which did not originate on Earth. No extraterrestrial life has yet been conclusively detected, although efforts are underway. Such life might ...
. 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 Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. Reproduction is a fundamental feature of all known life; each individual or ...
of all known living organisms and many viruses. DNA and
ribonucleic acid Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
(RNA) are
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
s; alongside proteins, lipids and complex carbohydrates (
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...
s), nucleic acids are one of the four major types of
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s 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. In natural DNA, each nucleotide is composed of one of four nucleobases ( cytosine guanine adenine or thymine , a
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by
covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
s 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 bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
s, according to
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
ing 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. Unnatural nucleobases, more hydrophobic than natural bases, 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 A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with se ...
.


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 Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
). :


Background

Earlier, the research group responsible for the hachimoji DNA system, headed by Harvard University chemist
Steven Benner Steven Albert Benner (born October 23, 1954) has been a professor at Harvard University, ETH Zurich, and the University of Florida where he was the V.T. & Louise Jackson Distinguished Professor of Chemistry. In 2005, he founded The Westheimer In ...
, 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.


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, 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". Creating new life forms may be possible, at least theoretically, with the new DNA system. 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."


Applications

NASA funded this research to "expand the scope of the structures that we might encounter as we search for life in the cosmos". According to
Lori Glaze Lori Glaze is an American scientist and the director of NASA's Science Mission Directorate's Planetary Science Division. She was a member of the Inner Planets Panel during the most recent Planetary Science Decadal Survey, and has had a role on t ...
of the Planetary Science Division of NASA, "Life detection is an increasingly important goal of NASA's planetary science missions, and this new work ith hachimoji DNAwill help us to develop effective instruments and experiments that will expand the scope of what we look for." Research team leader
Steven Benner Steven Albert Benner (born October 23, 1954) has been a professor at Harvard University, ETH Zurich, and the University of Florida where he was the V.T. & Louise Jackson Distinguished Professor of Chemistry. In 2005, he founded The Westheimer In ...
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." According to researchers, hachimoji DNA could also be used "to develop clean diagnostics for
human disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s, 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".


See also

* Abiogenesis *
Astrobiology Astrobiology, and the related field of exobiology, is an interdisciplinary scientific field that studies the origins, early evolution, distribution, and future of life in the universe. Astrobiology is the multidisciplinary field that investig ...
* Carbon chauvinism * Carbon-based life * Center for Life Detection Science * Earliest known life forms *
Extraterrestrial life Extraterrestrial life, colloquially referred to as alien life, is life that may occur outside Earth and which did not originate on Earth. No extraterrestrial life has yet been conclusively detected, although efforts are underway. Such life might ...
* ''Human Nature'' (2019 CRISPR film documentary) * Hypothetical types of biochemistry *
Nucleic acid analogue Nucleic acid analogues are compounds which are Analog (chemistry), analogous (structurally similar) to naturally occurring RNA and DNA, used in medicine and in molecular biology research. Nucleic acids are chains of nucleotides, which are compos ...
*
xDNA xDNA (also known as expanded DNA or benzo-homologated DNA) is a size-expanded nucleotide system synthesized from the fusion of a benzene ring and one of the four natural bases: adenine, guanine, cytosine, and thymine. This size expansion produ ...


References


Further reading

* Hypothesis paper.


External links


Astronomy FAQ - Why do we assume that other beings must be based on carbon? Why couldn't organisms be based on other substances?
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