Cynthia-3.0

The first synthetic organism with a minimal genome has been created

Alexander Ershov, N+1

A team of biologists led by Craig Venter managed to create an organism with the minimum possible genome, which was obtained completely synthetically. The basis of the minimal genome was the genome of the bacterium Mycoplasma mycoides, which scientists managed to "shrink" almost twice. Interestingly, of the 473 genes that are part of it, the role of 149 is now almost unknown. The work of Hutchison III et al. Design and synthesis of a minimal bacterial genome is published in the journal Science.

A colony of synthetic bacteria (scale size = 10 microns).
Electronic micrography J. Craig Venter Institute – VM.

The new work is a continuation of an earlier experiment, during which the same team managed to create a system of artificial genome synthesis. In 2010, scientists presented a strain of Mycoplasma mycoides JCVI-syn1.0, whose DNA was entirely obtained from thousands of small fragments — oligonucleotides obtained by chemical means. This DNA was introduced into the recipient cell, whose genome was previously destroyed. The main achievement of the researchers at that time was the development of a system that allows collecting individual oligonucleotides into long DNA fragments, correcting errors introduced by synthesis and eventually obtaining fully synthetic, "designer" genomes.

The paper published in 2010 dealt with the synthesis of a genome almost identical to the genome of a natural bacterium (with the exception of a small number of specially introduced "watermarks"). In the new work, the researchers took a step forward and were able to minimize the number of genes contained in the genome to an absolutely necessary minimum.

When determining the "minimality", two key requirements were imposed on the genome: 1) it had to allow the organism to reproduce itself (replicate) and 2) do it fast enough so that the low growth rate of colonies was not an obstacle to conducting experiments. To create a minimal set, scientists applied several parallel strategies. For example, mutagenesis by transposons, which allows you to selectively turn off individual genes by embedding a mobile genetic element in its sequence. If bacteria managed to survive in the presence of such an insertion in some gene, this gene was considered unnecessary for life. However, it turned out to be impossible to use such data directly due to functional duplication: if two genes can perform one vital function, then each of these genes seems unnecessary, although the removal of both leads to the death of the organism. As a result, the authors had to select the set of necessary genes manually, based on both transposon mutagenesis data and comparative genomics data.

The authors of the article position the resulting organism as a research platform for adding new functions. According to their idea, an organism with a minimal genome should be more predictable and effective for synthetic biology, which now relies on natural model organisms like E. coli or baker's yeast.

The concept of the minimum necessary genome was developed by Evgeny Kunin and Arkady Mushegyan back in 1996. According to their estimates at that time, based on a comparison of the newly sequenced genomes of Mycoplasma genitalium and Haemophilus influenzae, the minimum genome should include about 256 genes.

Portal "Eternal youth" http://vechnayamolodost.ru  25.03.2016