12 September 2014

How genes help to survive dehydration

Extreme mosquitoes will teach a person to do without water

Nadezhda Markina, "Newspaper.Ru»Russian scientists told the newspaper.

En" about the search for genes that allow the larva of the bell mosquito to withstand extreme dehydration. Now they are going to teach this to human cells, however, not in a living organism, but in culture. In this international project, the most high-tech part was performed by Russian researchers.

Some species can exist in conditions of such severe dehydration, which for the rest is completely incompatible with life, while their body loses more than 97% of the water contained in it. Biologists have found which genes and how to make this impossible possible, they published their results in the journal Nature Communications (Gusev et al., Comparative genome sequencing reveals genomic signature of extreme desiccation tolerance in the anhydrobiotic midge).

From the Russian side, specialists from the Institute of Fundamental Biology and Medicine of Kazan Federal University, the Faculty of Bioengineering and Bioinformatics, the Faculty of Biology and the Institute of Physico-Chemical Biology participated in the work. Belozersky MSU, as well as the Research Institute of Physico-Chemical Medicine.

Adaptation to dehydration gives organisms the ability to survive in a seemingly unsuitable environment: in the temperature range from -270 to +102 degrees, in a vacuum, with an extremely high dose of radiation, etc. Such an ability can also radically extend the life span, allowing you to experience tens or even thousands of years in a dried state before being saturated with water again and returning to active life.

In multicellular animals, this ability is rare. The largest and most complex representative of the fauna that can do this refers to insects, and this is the only example in the world of invertebrate arthropods. This is the larva of the ringworm mosquito Polypedilum vanderplanki. Bell mosquitoes are small insects flying over the water, they do not bite a person, and their larvae are familiar to all lovers of aquarium fish called moths.

The scientists compared the genomes of two species of bell mosquitoes: P. vanderplanki, which is able to tolerate dehydration, and P. nubifer, which does not possess this quality. The goal was to compare them and find what at the gene level provides resistance to dehydration.

About how the secret of the mosquito was revealed, "To the newspaper.Ru" was told by the first author of the article, a leading researcher and head of the laboratory "Extreme Biology" of the Institute of Fundamental Medicine and Biology of Kazan Federal University Oleg Gusev.

– Why are the mosquitoes the ringers?

– I have been engaged in extreme adaptations since I was a student, and my supervisor in Japan told me: choose champions, such animals that have no analogues. Mosquito larvae are a very interesting example of how super–stability can appear from scratch in a fairly short period of time. This is an analogue of X-men, where one or more mutations gave superpowers to living beings.

Ringer mosquitoes are a huge group, but for some reason, among 350 species living around the world, there is one that has developed the ability to survive complete dehydration (this is called cryptobiosis). It can survive even in a vacuum, in outer space.

This is a very interesting biological phenomenon – the emergence of an ideal defense from scratch. And this is an attractive model for comparative genomics to understand what had to change in order for such resistance to appear. In addition, this species is the most complex of cryptobionts, animals that can survive extreme dehydration.

P. vanderplanki lives in Africa, in Nigeria, where there are ten months of drought a year. Another species, P. nubifer, is a typical representative of the ringworm mosquitoes. These species are very similar, but if you dry the larvae of both, in one case it will be death, in the other – survival.

Their genomes are small and very similar to each other. But when dehydrated, special groups of genes were activated in the Nigerian mosquito, they multiplied in its genome and provided the synthesis of proteins that gave molecular protection. They are aimed at not storing water inside, but giving it out and replacing it with other molecules as a molecular shield.

– And what are these genes?

– We believe that the treasure chest has just opened a crack: wherever you look, amazing things are revealed to us in this organism. First, he has proteins that replace water during dehydration. They are called LEA proteins, these proteins usually accumulate in the seeds of plants, so that the seeds are resistant to drying. And it turned out that in animals capable of cryptobiosis, these proteins also appeared. Most likely, these genes were transferred to their genome by bacteria. And we have found confirmation of this.

The second group is the antioxidant genes. When dried, a large amount of free radicals accumulates in the cells. The antioxidant defense system fights against them, but it alone is not enough. In addition to the classic set of antioxidants, mosquitoes have developed an additional set of antioxidants in their genome, which are activated at the same time.

The third group is a group of enzymes that prevent the aging of proteins. With age, some amino acids are damaged, so proteins age, the cell ages and dies. But there is an enzyme that can partially restore damaged amino acids. And the mosquito, in addition to one such gene, has 13 additional genes.

In addition, bell mosquitoes are the only insects that have hemoglobin used for respiration. Their larvae are bloodworms, they are red. And they have hemoglobin genes, which are activated when dehydrated.

Finally, one of the most important components of sustainability is trehalose sugar. The water in the larva's body is replaced by a combination of proteins and sugar-trehalose during dehydration. And the genes of the enzyme that makes this sugar are also activated.

– Does your research have any practical application?

– When applying for one of the grant programs, one reviewer wrote: "Well, you have mosquitoes, how can you transfer them to people? It's one thing to dry mosquitoes, another to dry people...". But this comment is incorrect. Mosquitoes are a role model, biomimetics, when we try to use the abilities of another species for the benefit of humans.

We are planning and already conducting several post-genomic research areas. The first concerns a new approach in biotechnology. Using mosquito DNA, we have obtained gene constructs for transferring the desired gene and are already preparing to patent them for the synthesis of target proteins in mosquito cell culture.

Secondly, we are trying to teach animal cells (for example, oocytes) and humans to do without water.

Now we know what components are needed for this. As part of an international group based at Kazan University, we are working on this. It is especially gratifying that now our research and its various directions have received support from several Russian sources at once, including the Ministry of Education, the Russian Science Foundation and the Russian Foundation for Basic Research.

– And where can it be useful?

– Now biobanks for long-term storage of biomaterial, such as cord blood banks, are of great importance. Today they are very dependent on electricity. We are dealing with the possibilities of preserving cells in a viable state without water (which means that refrigerators are not needed in the future). Imagine what opportunities open up for, for example, military technologies: in the field, you can pour dried blood cells with water, and then use them.

– Tell us how you collaborated with foreign scientists and what part of the research was done in Russia.

– The whole story about the mosquito is very international. He lives in the only place in Nigeria. And 20 years ago, a Japanese scientist unearthed articles and organized a group dealing with cryptobiosis. After receiving my PhD, I worked in this group for some time, and we had the idea of a joint project.

But it so happened that the bulk of the sequencing and a significant part of the genetic analysis of the data was done in Russia, in the group of Maria Logacheva and Alexey Kondrashov.

This is a rather unique case when the most high-tech instrument part was implemented in Russia.

The laboratory formed at the expense of the megagrant, in fact, pulled out the entire genetic project. Our group at Kazan University carried out genome annotation, data comparison, and part of the sequencing and analysis of individual groups of genes were done in Japan.

But one of the locomotives of this work was Russian scientists, and I think this is very good.

Portal "Eternal youth" http://vechnayamolodost.ru12.09.2014

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