Zombie genes of olfactory receptors

Each genome contains pseudogens-DNA sequences that have once been full-fledged genes and have lost functionality as a result of mutations. Recently, Swiss scientists under the leadership of the associated professor of Lausanne University Richard Benton found that pseudo -Genes, despite the breakdown, can be quite functional [1]. The authors of the study proposed for them a new name - pseudo -pseudogens.

Coding DNA or RNA sequences are divided into triplets (semantic codons), each of which contains information about one amino acid. There are also stop codons, they indicate the point at which the protein synthesis should be stopped. Sometimes a mutation-a replacement of nucleotide or a shift of the reading frame-leads to the fact that the semantic triplet turns into a stop codon. In this case, the gene cannot encode full -size, full -fledged protein and becomes pseudo -gene.

Stop Codon, which arose in an inappropriate place, is called premature (Premature Termination Codon, then PTC). Pseudogens are often found among olfactory receptor genes. Perhaps this is the memory of the changes in the ecological niche. In a new environment, genes that allow you to recognize previous smells are not so important for survival, so they can lose a function.

Swiss scientists devoted their study to compare olfactory receptors in Drosophila melanogaster and closely related species D. Sechellia. IR75A receptors, located in neurons of certain sensitive hairs of Drusophiles, Sensillah AC2, perceive the smells of acids, including vinegar and propionic. Acetic acid is released when fruit rotting, and fruit flies must feel this smell vital.

It turned out that D. Melanogaster, the gene IR75A in perfect order, and D. Sechellia turned into pseudoen: the replacement of nucleotide made the amino acid Saa Stop-Codon Taa from the codon. Theoretically, D. Sechellia should not feel acetic acid, but they do not need it. D. Sechellia - the endemic species of Seychelles - is eating exclusively by the fruits of the noni plant ( Morinda Citrifolia ), which vinegar are practically not released.

Electrophysiological dimensions showed that D. Sechellia sensitals have really lost sensitivity to acetic acid, but they perceive the smells of other acids (propionic, oil and 2-oxopentan). Since the researchers found no other receptors except the IR75A, they could only assume that the IR75A pseudo-agency still encodes full-size protein and PTC is read as a semantic codon.

This assumption was confirmed. Functional pseudogen is an amazing phenomenon, it can be compared with a revived fossil or with a zombie that got up and went. In one of the notes, Richard Benton called the pseudo-agency “zombie gen” olfactory receptors [2].

Further studies have shown that reading the IR75A sequence through the premature stop codon occurs with the same effectiveness as if the original glutamine codon stood in this place. The effectiveness of protein synthesis depends on nucleotide located directly beyond the PTC. In D. Sechellia , this is a cytosine, its replacement with adenosine blocks reading stop codon.

In addition, the researchers found out that the IR75A pseudopseevodogen can operate in Sensillah not only D. Sechellia , but also D. Melanogaster , both in Sensille of AC2 and other neurons, so through reading is not specific for a certain type of disconnial neurons. However, in non-nenary cells, for example, in glia, PTC is not read, so cell specificity still takes place.

The sensitivity of the IR75A D. Melanogaster receptors, the related appearance of D. Simulans and D. Sechellia vary. The first two species feel the smells of acetic and propionic acid, and D. Sechellia smell propione, oil and 2-oxipntan. According to researchers, the difference in perception is caused by differences in genetic sequence. Pseudopseevodogen, in addition to PTC, has seven more mutations leading to amino acid replacements. If you make these mutations in IR75A D. Melanogaster, the sensitivity of its receptor will change, and transgenic flies will perceive the same smells as D. Sechellia.

Since there are a lot of pseudogens in the genome, the researchers suggested that the functionality of IR75A D. Sechellia is no exception. There may be other pseudo -agencies in which PTC is read. Scientists began to look for such sequences and found pseudo -henchodes of several olfactory receptors in D. Melanogaster and representatives of the Tasman group Drusophile. Thus, the phenomenon of functional olfactory pseudo -gene is not limited by either a specific type or a specific receptor.

Cases of reading PTC are known for viruses, but in eukaryotes in natural conditions they are described for the first time. Since the researchers have already discovered four such cases, this process is not exceptional and effective enough to ensure pseudogens functionality. How exactly is the reading through PTC, scientists do not yet know. Perhaps in neurons there is a special molecular machinery for this.

Richard Benton and his employees suggest that functional pseudo -agencies are wider than it is customary to think. They intend to continue the experimental study of hundreds of pseudo -gene containing PTCs, not only in insects, but also in other organisms, in particular, in humans.

Natalia Reznik

1. Prieto-Godino LL, Rytz R., Bargeton B., Abuin L., Arguello Jr, Dal Poraro M., Benton R. Olfactory Reception Pseudo-pseudogenes // NATURE, 539 (7627): 93-97,, 93-97, DOI: 10.1038/Nature19824

2. Www.hfsp.org/frontier-science/Awardees-articles/%E2%80%9Czombie%E2%80%9D-genes-olfactory-system