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Home https://server7.kproxy.com/servlet/redirect.srv/sruj/smyrwpoii/p2/ Science https://server7.kproxy.com/servlet/redirect.srv/sruj/smyrwpoii/p2/ Researchers make their own genome for E. coli, compress its genetic code

Researchers make their own genome for E. coli, compress its genetic code



  Like any other E. coli but different.
Enlarge / Like any other E. coli but different.

Genetic code is the basis of all life, allowing information in DNA to be translated into proteins that perform most cell functions. Yet it is … a mess. Life usually uses a packet of about 20 amino acids, while the genetic code has 64 possible combinations. This discrepancy means that the surplus is widespread and many species have evolved in terms of what would otherwise be a universal genetic code.

So the code itself is significant, or it's like a historical incident closed by events. in the distant evolutionary past? The answer to this question was not an option until recently, as the individual codes appear in hundreds of thousands of places in the genomes of the simplest organisms. But because our ability to make DNA increase, it has been possible to synthesize whole genomes from scratch, allowing the rewriting of the genetic code to wholesale.

The researchers now declare that they have processed the bacterial genome ) to get rid of excess genetic code. The resulting bacteria grow a bit slower than the normal strain, but otherwise they are hardly different from their non-synthetic peaks.

Codes and surplus

The genetic code is written in sets of three DNA bases. Each of the three positions may contain any of the four bases, meaning that there are 4 x 4 x 4 possible combinations or 64. In contrast, there are only 20 amino acids while at least one of the other codons should be used to tell the cell stops translating the code. This leaves a discrepancy of 43 codes that are not strictly necessary. The cells use these additional codes as a surplus; instead of one stop code, most genomes use three. Eighteen of the 20 amino acids are encoded with more than a set of three bases; two have up to six possible codes.

Is this worthless? The answer is "sometimes". For example, many DNA sequences make a double load encoding both protein and regulatory information that controls gene activity or allows the formation of specific RNA structures. The flexibility of surplus makes it easier for a sequence to serve two purposes. Surplus may also allow fine tuning of gene activity, as some codes are translated into proteins more efficiently than others. These factors suggest that the surplus of genetic code may have evolved to be essential to an organism.

Testing whether this is the case, however, is a little nightmare. Even the most compact genomes have hundreds of genes ( the E. coli strains have between 4000 and 5500) and all individual codes can occur multiple times within each. Editing each one is possible, but it will take a long time.

So the researchers simply transcended things on a computer. Focusing on one of the amino acids that have multiple redundant codes, they changed the sequence so that more than 1

8,000 individual uses of two of the codes were replaced with an unnecessary option. The synthetic genome is just a matter of dividing pieces that can be ordered from a DNA synthesizer. This is easier than it sounds, according to one of the researchers (and regular reader of Ars) Wolfgang Schmidt. "With such a project where you ask questions about the rules of the genetic code, you have to commit yourself at some point to order synthetic DNA of genome value," he told Ars, "which is quite a large financial commitment rather than an easy push button "However, it is necessary to assemble.

Some assembling is needed

Unfortunately, there is a big difference between what a DNA synthesis engine can produce and the genome of several million bases. The group had to perform a whole assembling process by connecting small pieces into a large segment in a cell and then transferring it to another cell that had an overlapping large segment. "My biggest surprise was how well the assembly process works," Schmidt said. "The success rate at each stage is very high, which means we could do most of the work with standard techniques."

During the process there were several places where the synthetic genome ended with problems – at least in one case where two major genes overlap. But researchers have managed to correct their version to overcome the problems they have identified. The last genome also had several errors that occurred during the assembly process, but none of them changed the three base codes that were targeted.

After all, she was working. Instead of using 61 of the 64 potential amino acid codes, the new organism, called Syn61, only uses 59. The researchers could then erase the genes normally allowed by E. coli to use redirected codes. Generally these genes are essential; in Syn61, they can be deleted without any problem. This does not mean that the Syn61 strain is good; grew slower than normal peers. But this is probably the result of all the previously described cases where the DNA sequences perform more than one function. It is possible, over time, that the strain develops back to normal growth.

In addition to answering questions about basic biology, the Syn61 strain may ultimately be useful. There are many more amino acids than 20 lifetime users and many of them have interesting chemical properties. To use them, however, we need backup genetic codes that can be redirected to artificial amino acids – just what this new job has provided.

Nature 2019. DOI: 10.1038 / s41586-019-1192-5 (for DOIs).


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