In 2014, scientists engineered Escherichia coli to incorporate new bases they called 'X' and 'Y' in addition to adenine-thymine (A-T) and guanine-cytosine (G-C). Now it has been demonstrated that these synthetic base pairs can be transcribed into RNA and used to produce a protein containing "unnatural" amino acids.
The addition of the new bases could increase the amount of amino acids from 20 to a possible total of 172.
A semi-synthetic organism that stores and retrieves increased genetic information (DOI: 10.1038/nature24659) (DX)
Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Previous efforts to generate such semi-synthetic organisms culminated in the creation of a strain of Escherichia coli that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum tricornutum, imports the requisite unnatural triphosphates from its medium and then uses them to replicate a plasmid containing the unnatural base pair dNaM–dTPT3. Although the semi-synthetic organism stores increased information when compared to natural organisms, retrieval of the information requires in vivo transcription of the unnatural base pair into mRNA and tRNA, aminoacylation of the tRNA with a non-canonical amino acid, and efficient participation of the unnatural base pair in decoding at the ribosome. Here we report the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with two different unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient decoding at the ribosome to direct the site-specific incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein. The results demonstrate that interactions other than hydrogen bonding can contribute to every step of information storage and retrieval. The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions.
Previously: Scientists Engineer First Semisynthetic Organism With Three-base-pair DNA
Related: How Scientists Are Altering DNA to Genetically Engineer New Forms of Life
Related Stories
Researchers at The Scripps Research Institute (TSRI) claim to have created the first stable semisynthetic organism with extra bases added to its genetic code. The single-celled organism is also able to continually replicate the synthetic base pair as it divides, which could mean that future synthetic organisms may be able to carry extra genetic information in their DNA sequences indefinitely.
The cells of all organisms contain genetic information in their DNA as a two-base-pair sequence made up of four molecules – A, T, C, G (Adenine, Cytosine, Thymine, and Guanine). Each of these is known as a nucleotide (consisting of a a nitrogenous base, a phosphate molecule, and a sugar molecule) and are specifically and exclusively paired, so that only A is coupled to T and C is coupled with G. These nucleotides are connected in a chain by the covalent (electron-coupled) bonds between the sugar of one nucleotide and the phosphate of the next, which creates an alternating sugar-phosphate "backbone."
The team from TSRI have added two synthetic bases that they call "X" and "Y" into the genetic code of a E.coli carrier organism – a single-cell bacteria – and then chemically tweaked it to live, replicate, and survive with the extra DNA molecules intact.
The paper is available via PNAS:
Yorke Zhang, et al.,A semisynthetic organism engineered for the stable expansion of the genetic alphabet (DOI: 10.1073/pnas.1616443114)
New Natural Selection: How Scientists Are Altering DNA to Genetically Engineer New Forms of Life
Before human beings wrote books or did math or composed music, we made leather. There is evidence hunter-gatherers were wearing clothes crafted from animal skins hundreds of thousands of years ago, while in 2010 archaeologists digging in Armenia found what they believed to be the world's oldest leather shoe, dating back to 3,500 B.C. (It was about a women's size 7.) For a species sadly bereft of protective fur, being able to turn the skin of cows or sheep or pigs into clothing with the help of curing and tanning would have been a lifesaving advance, just like other vital discoveries Homo sapiens made over the course of history: the development of grain crops like wheat, the domestication of food animals like chickens, even the all-important art of fermentation. In each case, human beings took something raw from the natural world—a plant, an animal, a microbe—and with the ingenuity that has enabled us to dominate this planet, turned it into a product.
[...] Modern Meadow's microbes can produce collagen much faster than it would take to raise a cow or sheep from birth, and the company can work with brands to design entirely new materials from the cell level up. "It's biology meets engineering," says Andras Forgacs, the co-founder and CEO of Modern Meadow. "We diverge from what nature does, and we can design it and engineer it to be anything we want."\
That is the promise of synthetic biology, a technology that is poised to change how we feed ourselves, clothe ourselves, fuel ourselves—and possibly even change our very selves. While scientists have for decades been able to practice basic genetic engineering—knocking out a gene or moving one between species—and more recently have learned to rapidly read and sequence genes, now researchers can edit genomes and even write entirely original DNA. That gives scientists incredible control over the fundamental code that drives all life on Earth, from the most basic bacterium to, well, us. "Genetic engineering was like replacing a red light bulb with a green light bulb," says James Collins, a biological engineer at the Massachusetts Institute of Technology and one of synthetic biology's early pioneers. "Synthetic biology is introducing novel circuitry that can control how the bulbs turn off and on."
The article discusses a number of topics, including microbe-grown collagen for leather, Genome Project-write, synthetic cells, a company using yeast to make perfumes and other products, and the falling (but still high) cost of DNA synthesis.
Related: Project to Synthesise Genes Mooted
Scientists Engineer First Semisynthetic Organism With Three-base-pair DNA
Scientists Create Independent Synthetic Cell With Smallest Known Genome
NASA-Funded Research Creates DNA-like Molecule to Aid Search for Alien Life
In a research breakthrough funded by NASA, scientists have synthesized a molecular system that, like DNA, can store and transmit information. This unprecedented feat suggests there could be an alternative to DNA-based life, as we know it on Earth – a genetic system for life that may be possible on other worlds.
This new molecular system, which is not a new life form, suggests scientists looking for life beyond Earth may need to rethink what they are looking for. The research appears in Thursday's edition of Science Magazine.
[...] The synthetic DNA includes the four nucleotides present in Earth life – adenine, cytosine, guanine, and thymine – but also four others that mimic the structures of the informational ingredients in regular DNA. The result is a double-helix structure that can store and transfer information.
[Steven] Benner's team, which collaborated with laboratories at the University of Texas in Austin, Indiana University Medical School in Indianapolis, and DNA Software in Ann Arbor, Michigan, dubbed their creation "hachimoji" DNA (from the Japanese "hachi," meaning "eight," and "moji," meaning "letter"). Hachimoji DNA meets all the structural requirements that allow our DNA to store, transmit and evolve information in living systems.
Also at NYT, Discover Magazine, and ScienceAlert.
Hachimoji DNA and RNA: A genetic system with eight building blocks (DOI: 10.1126/science.aat0971) (DX)
Related: Scientists Add Letters X and Y to DNA Alphabet
Scientists Engineer First Semisynthetic Organism With Three-base-pair DNA
How Scientists Are Altering DNA to Genetically Engineer New Forms of Life
Synthetic X and Y Bases Direct the Production of a Protein With "Unnatural" Amino Acids
(Score: 0) by Anonymous Coward on Saturday December 02 2017, @03:17AM (14 children)
It's well known that genetic drift makes it difficult to isolate genetic mechanisms from being propagated to other organisms using the same genetic codes.
However, if we posit an organism where all changes to the genotype are made using DNA sequences not found in nature, then perhaps that would provide a form of damage control.
My $0.02, YMMV, etc.
~childo
(Score: 3, Interesting) by JoeMerchant on Saturday December 02 2017, @04:36AM (13 children)
I don't feel like the artificial genes are any better controlled, but they certainly are more identifiable - so we'll know what kills us all came from us.
There is probably a weakness to the artificial base pairs, otherwise they would have evolved up into normal use along with the common 4 - so, a billion years from now, they may fade away.
🌻🌻 [google.com]
(Score: 4, Insightful) by JNCF on Saturday December 02 2017, @05:11AM (2 children)
Not necessarily; evolution is a bloody mess and it doesn't solve problems in the best way possible, merely incrementally better ways.
(Score: 2) by frojack on Saturday December 02 2017, @07:34AM (1 child)
Never the less, it does seem odd that ALL life on the planet use only the same 4 bases. Given that we have highly isolated life forms cooking in every biological soup in every corner of the planet, it seems you could have bet some odd ball life form would have found it advantageous to encode something unusual.
If we can imagine it and do it, how long till it becomes mandatory?
No, you are mistaken. I've always had this sig.
(Score: 2) by c0lo on Saturday December 02 2017, @10:09AM
Nope. If this is all you can find to eat, you aren'r going to have material to build your DNA from something else.
https://www.youtube.com/watch?v=aoFiw2jMy-0 https://soylentnews.org/~MichaelDavidCrawford
(Score: 3, Interesting) by sjames on Saturday December 02 2017, @07:39AM (7 children)
One help is that the bacteria can be made to depend on amino acids that they won't find in nature. If they escape the lab they starve.
(Score: 3, Interesting) by takyon on Saturday December 02 2017, @07:45AM (3 children)
They might just mutate to remove inhibitory X and Y bases.
[SIG] 10/28/2017: Soylent Upgrade v14 [soylentnews.org]
(Score: 2) by sjames on Saturday December 02 2017, @08:07AM (2 children)
That's much less likely when there's no gradient between the 'good' environment and the fatal one. It's also fairly easy to detect a contaminated culture. Transfer a bit to a conventional growth medium. If anything at all grows, destroy it and the tested culture.
(Score: 2) by JoeMerchant on Saturday December 02 2017, @06:05PM (1 child)
You are talking about best practices. 7 billion people on the planet, say that someday one in a thousand is capable of genetic engineering... that leaves 7 million genetic engineers, if only one in a million is stupid enough to be careless about best practices, that's 7 ground zeroes for escaped bad actors...
🌻🌻 [google.com]
(Score: 2) by takyon on Sunday December 03 2017, @10:22AM
The focus going forward should be on bolstering human defenses against biological agents rather than trying to regulate amateur biology and suppress citizen science, which will only turn ugly fast.
[SIG] 10/28/2017: Soylent Upgrade v14 [soylentnews.org]
(Score: 2) by JoeMerchant on Saturday December 02 2017, @06:02PM (2 children)
The bacteria can be attempted to be made to depend on amino acids that they won't find in nature. What they actually do after exchanging some DNA in the wild is anybody's guess.
🌻🌻 [google.com]
(Score: 2) by sjames on Saturday December 02 2017, @06:22PM (1 child)
But they won't exchange DNA in the wild since in the wild they will die
(Score: 3, Insightful) by JoeMerchant on Saturday December 02 2017, @10:33PM
And the wild never gets into the lab where the exotic food is? In real life?
🌻🌻 [google.com]
(Score: 2) by maxwell demon on Saturday December 02 2017, @09:29AM (1 child)
It also means we'd have a better chance to fight those things, by designing a poison that attacks specifically those "unnatural" amino acids.
The Tao of math: The numbers you can count are not the real numbers.
(Score: 2) by JoeMerchant on Saturday December 02 2017, @06:08PM
True, though (however unlikely) if our artificial base pairs are somehow superior to the existing ones, we can have a whole new field of study about the weird things they can do that natural life cannot. We've been studying the basic 4 for thousands of years indirectly, 50 years directly and are just starting to get a handle on them....
🌻🌻 [google.com]
(Score: 0) by Anonymous Coward on Saturday December 02 2017, @10:57AM
Aside from the cool factor, "We invented a new variation on life", are there any potentially useful applications for this new form of DNA? Maybe this is the start toward nano assemblers (or the start toward grey goo)?