18 July 2011

Editing genomes

The first step to rewriting the genetic code has been takenTape.
Roo

Scientists have developed a technology that allows the "streaming method" to edit DNA. Using the new method, experts were able to replace all sequences of a certain type in the E. coli genome with an alternative variant and assign a new value to the "discarded" sequence. The researchers' work has been published in the journal Science (Isaacs et al., Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement), and the Nature News portal (Genomes edited to free up codons) writes briefly about the work.

Genetic information about an organism is recorded in its DNA – a linear polymer molecule consisting of four types of "letters" (biologists call them nucleotides) – they are designated as A, T, G and C. Certain combinations of triples of these "letters" (codons) encode certain amino acids – elementary "bricks" that make up proteins. The correspondence between the triples of nucleotides and amino acids is set by the genetic code. One of its characteristics is redundancy: there are more combinations of three nucleotides than their corresponding amino acids.

The authors of the new work relied precisely on the property of redundancy of the genetic code. In their work, they decided to replace all the so-called stop codons of one type with stop codons consisting of a different combination of nucleotides. Stop codons encode not an amino acid, but one of the "punctuation marks" that enzymes need to correctly read the genetic code. In this case, this punctuation mark was a dot.

Most organisms use three types of stop codons - TAG, TAA and TGA. Scientists replaced all TAG sequences (there are 314 of them in the Escherichia coli Escherichia coli genome) with TAA. At the first stage of the work, the researchers artificially synthesized 314 short fragments of E.coli DNA, normally containing the TAG sequence – however, in the newly synthesized fragments, the tags were replaced with TAA. To insert artificial sequences into the genome of bacteria, specialists drove them inside the cells using current discharges (this is a standard molecular biological technique). As a result, the scientists obtained 31 lines of E.coli, each of which carried 10 modified sequences, and one line with four modified stop codons.

At the next stage of the experiment, the scientists tried to ensure that all the modified stop codons were in the genome of one cell. The researchers consistently "crossed" bacteria from the lines obtained at the first stage with each other – at the same time, the bacteria exchanged genetic material, and in some cases, DNA regions containing altered stop codons participated in this exchange.As a result, the authors managed to obtain an E.coli line, in which all the TAG stop codons were replaced with TAA.

Next, the scientists cut from the DNA of these bacteria a gene encoding an enzyme that recognizes the TAG sequence as a stop codon. Thus, the researchers obtained an organism suitable for the sequence of tags in its genetic code to correspond to a certain new amino acid – in previous works, other teams of authors have already created such amino acids and the enzymes necessary for reading them.

The technology created by the authors of the new work will help scientists in the future to create organisms with a slightly different genetic code than other living beings. Theoretically, such organisms will be resistant to viruses, since the latter exploit the protein-synthesizing apparatus of the host cell, "sharpened" under the "correct" genetic code. Viruses will not be able to use the protein-synthesizing apparatus of cells with a modified code.

Portal "Eternal youth" http://vechnayamolodost.ru18.07.2011

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