Scientists have long wondered: can they create a full-fledged synthetic life form? Biologist Anthony José introduced the concept of a cellular code, the knowledge of which is necessary to obtain an artificial organism.
At present, researchers have just begun to produce artificial life forms by reassembling the genomes of unicellular microorganisms. In particular, in March last year, an article appeared in one of the specialized publications in which scientists described the process of creating a mycoplasma bacterium with the minimum possible number of genes. To get the desired result, scientists alternately inserted fragments of the altered genome, which was almost half the size of the original, into the recipient cell with the destroyed DNA.
This year, American researchers from Johns Hopkins University managed to obtain yeast with artificial chromosomes, from which useless and defective genes were removed. In addition, the scientists managed to break the genetic code by changing the triplets of the TAG proteins to TAA. Due to this, the organisms got rid of the extra fragment that served the TAG codons.
While some researchers are trying to create unicellular organisms free from genetic debris, at the same time, other scientists are trying to make changes in the way proteins are encoded by a DNA sequence. At the moment, progress in this direction is more than modest. The little that has been done is to diversify the DNA alphabet. A few letters were added to the four already existing nucleotide letters. One of the scientific articles talks about how an international group of researchers managed to insert artificial nucleotides Y, X into the genome of E. coli. In spite of the fact that something similar was done before, the researchers managed to ensure that the bacteria retained a synthetic part in their DNA, but while successfully developing.
However, this is just the first step towards a full-fledged artificial organism. In the next step, scientists intend to force artificial nucleotides to encode amino acids. In E. coli, synthetic proteins Y, X were placed in a safe part of the genome, outside the coding sequences of genes. Otherwise, new peptides would simply disrupt the process of protein synthesis. The cell would simply not know which amino acid this or that codon (YGC or ATX) was responsible for. Biologists have yet to create a new transport RNA that will be able to recognize such triplets and insert a certain amino acid into the growing peptide sequence.
But even under such conditions, such an organism can hardly be called artificial. At the same time, scientists understand what their next actions will be. A synthetic organism will receive not only new nucleotides, but also new amino acids, which either do not occur at all, or are extremely rare inside the cell. Scientists are well aware that all triplets of nucleotides are encoded by only twenty standard amino acids. Some other amino acids, including selenocysteine, can be incorporated into the protein under certain conditions. Thanks to the additional letters of the genetic code, it will be possible to enrich the protein and form codons that will correspond to the new amino acids.
Despite the fact that synthetic biology has made some progress, researchers still do not know exactly what information is important to obtain an organism with the given characteristics. The DNA sequence is just a starting point. All cells of a plant or animal contain the same genome, but in the course of development of organisms, the cells are delimited, in other words, they perform different functions. In this process, secondary (so-called epigenetic) regulation plays an important role, during which certain genes are turned off or activated by compounds. Ultimately, one cell can transform into a fibroblast and another into a neuron.
Anthony José, a biologist at the University of Maryland, is studying how nongenetic information defines an organism. The researcher proposed the concept of a cellular code, which is enclosed in biological molecules located in three-dimensional space. These molecules are needed to recreate the rest of the organism. To store this information, all the cells of a complex organism are not needed; several or even one cell will be enough. For organisms that reproduce sexually, such a repository is the zygote (this is a cell that is formed after the fertilization of a female gamete with a sperm).
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According to the researcher, in order to decipher the cellular code, it is necessary to study the entire cycle of the organism's reconstruction. In other words, it is necessary to consider the development of a living organism and its reproduction as a single process. To fully understand how this works, it is not enough to decipher DNA.
During the formation of a zygote, the formation of a new organism is influenced not only by the DNA obtained from the oocyte and the sperm, but also by the cytoplasm of the gamete. Substances that accumulate during gamete maturation (mRNA, proteins, transcription factors) can cause the maternal effect. They are present in the early stages of development of the embryo and are even capable of killing it (this is typical for the May beetle beetles). The spatial structure of these substances also plays a certain role. In particular, they form the body axes in insects and determine the curl of shells in molluscs.
The scientist will propose the following scheme: a cell that has biological macromolecules and other compounds, in the process of interacting with nutrients, signaling molecules and temperature (that is, external factors), passes into another state, which, in turn, affects the environment. In a similar way, the entire system goes through a certain number of cycles, while accumulating new substances. The new stage depends on the previous one, so it can be predicted.
Jose is worried that biologists still do not know the entire cellular code of the simplest organism, but they, working with DNA, nevertheless, have already set about creating a semi-artificial life form. According to the researcher, such manipulations with genetic material resemble the replacement of parts in some mechanism, so they can be very risky from the point of view of ethics.
To decipher the cellular code, the biologist proposes to compare the internal characteristics of zygotes in a series of generations of the simplest microorganisms, for example, unicellular algae. For these purposes, semi-artificial bacteria with a minimal genome may also be suitable. By studying the paternal or maternal effect, it will be possible to establish significant external factors. And the study of the spatial arrangement of important molecules can be carried out using systematic biochemical and molecular analysis using fluorescent molecules.