Nine years ago, American scientists led by geneticist Craig Venter announced that they created the first
However, a few years later, scientists recognized thatthe bacterial genome was not really radically altered. Despite this, the work of scientists marked the beginning of a new direction in genetics, which is engaged in the creation of organisms with fully edited DNA.
E. coli E. coli
Scientists from thethe GP-write project - they have already managed to create artificial copies of 2 of the 16 chromosomes that make up the genome of one baker's yeast strain. But the DNA of Mycoplasma mycoides includes only 1.08 million base pairs, and the yeast chromosomes are less than 1 million. E. coli, with which genetics from the Laboratory of Molecular Biology of the Medical Research Council of England in Cambridge worked, contains 4 million bases.
Researchers led by doctor jason chinsmashed these 4 million bases of Escherichia coli into 37 fragments and synthesized them. The resulting sample is similar to its natural counterparts, but survives due to a smaller set of genetic tools.
What is DNA and why to synthesize it
First of all, it is necessary to understand what DNA is. This is deoxyribonucleic acid, which is the hereditary material of man and all living organisms.
Almost every cell in the human body has one andthe same DNA. Most of the deoxyribonucleic acid is in the cell nucleus (it is called nuclear DNA), but it is present in a small amount in the mitochondria.
Information in DNA is stored as a code consistingOf the four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T). The human genome consists of about 3 billion bases, and more than 99% of these bases are the same for all people. Their order and sequence determines how the body is built and maintained - just as the letters of the alphabet are built in a certain order, forming words and sentences.
DNA bases mate with each other -for example, A with T and C with G to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together the base, sugar and phosphate are called a nucleotide.
Nucleotides are located in the form of two long strands that form a double helix - in this form we are used to imagining DNA.
The structure of the double helix is somewhat reminiscent of a ladder: base pairs form steps, and sugar and phosphate molecules form vertical side portions.
DNA folded into a cell contains instructionsnecessary for its functioning. For example, when a cell needs more protein to grow, it reads the DNA that encodes the desired protein. Such compounds are called codons and are written in three letters — for example, TCG and TCA.
Almost all forms of life, from jellyfish to humans,use 64 codons. But many of them do the same job or repeat their functions. A total of 61 codons form 20 naturally occurring amino acids that can be linked together, like beads on a string, to create any protein in nature. Three more codons are a kind of inhibitor - they tell the cell when the protein is ready, and it needs to stop generating it.
Codons are used to identify amino acids,part of the proteins they produce. TCA, for example, defines serine, which means "extract this amino acid from cell broth and attach it to the protein that the cell produces." AAG defines lysine. TAA means stopping the addition of amino acids to a growing protein. But AGT also means serine, like AGC, TCT, TCC and TCG. If nature were effective, it would use 20 codons for 20 amino acids, plus one for “stopping”.
The researchers tried to create such an optimized organism.
What exactly did genetics do
A group of scientists from Cambridge studied the wholegenetic code of E. coli strain and analyzed the functions of all codons. After that, the researchers of the serine codon replaced the TCG with AGC, each TCA (also serine) with AGT and each TAG (stop codon) with TAA.
In total, they contributed to the DNA of E. coli 18 214 edits - the resulting genome was the largest DNA block ever created by artificial fusion. On paper, the recording of the edited genome looks like the researchers decided to replace one very common word in a digital copy of the novel War and Peace.
However, the most difficult work was to collectchemical copy of the rewritten genome and exchange it for the original inside living organisms. This work took scientists about two years: when each synthetic fragment replaced the original code, the researchers observed whether the bacteria would function or die.
"There are many possible ways to transcodegenome, but many of them are problematic: the cell dies. For example, supposedly synonymous codons can produce different amounts of protein, and sometimes proteins with unexpected characteristics that kill a cell. "
Jason Chin, lead author
Researchers have discovered a recoding schemewhich allowed replacing the original code with an artificial one and keeping E. coli alive, despite using 59 codons instead of 61 for generating amino acids and two, rather than 3 codons, to stop this process.
Thus, scientists were able to reduce the numbercodons from 64 to 61. This is a new record - until now geneticists managed to create the bacterium Escherichia coli, which could survive with only 63 codons instead of 64.
Where it leads
The main purpose of creating an edited genome -the ability to give codons the ability to generate one of the hundreds of amino acids, in addition to 20, laid down by nature. This will make it possible to synthesize new enzymes and other proteins.
"Nature has given us a limited set of enzymes,whose properties we have learned to use for performing complex tasks, ranging from the production of cheese and fruit juice, to the manufacture of biofuels and the detection of markers in biological tests. We can do all this with a set of 20 amino acids - imagine what opportunities we can get from using 22 or more amino acids, ”said Stat Ellis, an expert in synthetic biology at Imperial College London.
Among these opportunities is the creation of newfood, the emergence of new opportunities for industry, and, most importantly, the creation of bacteria resistant to viruses. This will allow pharmacists to create drugs that will more effectively deal with viruses and bacteria.
Did the discovery of scientists these opportunities? Not. But it made it possible to go far ahead in an attempt to create a fully synthetic genome of a living organism with functions different from the original ones.
"They raised the field of synthetic genomics onthe new level, not only successfully collecting the largest synthetic genome ever created, but also making the greatest changes to it, ”Alice concluded in an interview with The Guardian.