Satan can code
The DNA of life on Earth naturally stores its information in just four key chemicals—guanine, cytosine, adenine and thymine, commonly referred to as G, C, A and T, respectively.
Now scientists have doubled this number of life’s building blocks, creating for the first time a synthetic, eight-letter genetic language that seems to store and transcribe information just like natural DNA.
In a study published on 22 February in Science, a consortium of researchers led by Steven Benner, founder of the Foundation for Applied Molecular Evolution in Alachua, Florida, suggests that an expanded genetic alphabet could, in theory, also support life.
“It’s a real landmark,” says Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California. The study implies that there is nothing particularly “magic” or special about those four chemicals that evolved on Earth, says Romesberg. “That’s a conceptual breakthrough,” he adds.
Normally, as a pair of DNA strands twist around each other in a double helix, the chemicals on each strand pair up: A bonds to T, and C bonds with G.
For a long time, scientists have tried to add more pairs of these chemicals, also known as bases, to this genetic code. For example, Benner first created ‘unnatural’ bases in the 1980s. Other groups have followed, with Romesberg’s lab making headlines in 2014 after inserting a pair of unnatural bases into a living cell.
But the latest study is the first to systematically demonstrate that the complementary unnatural bases recognize and bind to each other, and that the double helix that they form holds its structure.
https://www.scientificamerican.com/article/4-new-dna-letters-double-lifes-alphabet/
==“Alien” DNA Makes Proteins in Living Cells for The First Time
Expanded genetic alphabet could allow for the production of new protein-based drugs==
Life has spent the past few billion years working with a narrow vocabulary. Now researchers have broken those rules, adding extra letters to biology's limited lexicon.
Chemist Floyd Romesberg of the Scripps Research Institute in La Jolla, California, and his colleagues manipulated Escherichia coli bacterial cells to incorporate two types of foreign chemical bases, or letters, into their DNA. The cells then used that information to insert unnatural amino acids into a fluorescent protein.
Organisms naturally encode heritable information using just four bases: adenine (A), thymine (T), cytosine (C) and guanine (G). These form pairs that hold together DNA’s double helix, and different three-letter sequences code for each of the 20 amino acids that make up the proteins in living cells. The new work is the first to show that unnatural bases can be used to make proteins within a living cell.
The achievement, Romesberg says, shows that synthetic biology—a field focused on imbuing organisms with new traits—can accomplish its goals by reinventing the most basic facets of life. “There is no biological system so fundamental and more intimately related to what we are than information storage and retrieval,” he says. “What we’ve done is design a new part that functions right alongside the existing parts and can do everything they do.”
ALPHABET EXTENSIONS
Several teams are attempting to expand the genetic code. The four natural DNA bases can be arranged in 64 different three-letter combinations, called codons, that specify amino acids. But redundancy in this code—for instance, CGC, CGA, CGG and CGT all stand for the amino acid arginine—means that nearly all proteins needed for life are made of just 20 amino acids.
Researchers including geneticist George Church of Harvard Medical School in Boston, Massachusetts, are working on repurposing redundant codons to specify new amino acids. Romesberg’s group is exploring a different strategy: adding an entirely new base pair into DNA. That would vastly increase the number of possible codons, in theory giving cells the ability to edoit more than 100 extra amino acids. Church still believes that his own approach is more practical for most applications, he describes the new work as a “milestone in exploring the fundamental building blocks of life”.
Researchers first imagined an expanded genetic alphabet in the early 1960s. The first big success came in 1989, when a team led by chemist Steven Benner, then at the Swiss Federal Institute of Technology in Zurich, forged DNA molecules containing modified forms of cytosine and guanine. These “funny” DNA letters, as Benner has called them, could replicate and make RNA and proteins in test-tube reactions.
https://www.scientificamerican.com/article/ldquo-alien-rdquo-dna-makes-proteins-in-living-cells-for-the-first-time/
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