Large genome protects from mutations

In the opinion of L.I. Patrushev and I.G. Minkevich, specialists of the M.M. Shemiakin and Yu.A. Ovchinnikov Institute of Bio-organic Chemistry and the G.K. Skriabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, one of previously unknown functions of noncoding sections lies in protection from mutations of the genes and regulatory areas of genome needed to the organism.

With various species, the size of genome differs by more than 200,000 times, the genome size does not correspond to biological complexity of the species. Gigantic genomes exceeding the human ones by 34 times, belong to the urodelous amphibian – olm (Proteus) and a South-American lungfish. The leading position among the plants is kept by representatives of the liliaceous (lilies, hyacinths, daffodils, etc.). There are relatively few “needed” genes in gigantic genomes, the major volume is occupied by a noncoding DNA. The total quantity of DNAs in a single set of chromosomes is customaty to designate by the Latin letter C, therefore discrepancy between the genome size and biological complexity of a living organism possessing it was called the C paradox. The reasons are still unknown why some species have an extremely large genome or the functions that perform successions of noncoding DNAs of higher organisms, although researchers are certainly making various assumptions. In opinion of the Russian biologists, noncoding sections create an additional level of protection from chemical mutagens for coding sections.

Under ordinary conditions, mutagens are not in deficiency. Numerous substances are being constantly formed in the organism’s cells, for example active forms of oxygen, derivatives of basic nitrogens or oestrogen metabolites, under the action of which hundreds of thousands of injuries originate and are simultaneously present in chromosomal DNA. If the system intended for the DNA repair does not work in proper time, mutations will occur. As it has tuned out, the organism utilizes one more level of protection for genome safety. In particular, the genome size increase can reduce frequency of injuries of genes needed to the organism.

The researchers have determined that the injury frequency depends on the size of genome: the larger the size it, the lower the frequency is. So, large genome serves protection from injuries. Coding successions also protect each other: if mutation has affected one section, it bypasses another one. However, in this case some other gene is injured. It is much more convenient if the protective function is performed by the sections not containing important information. Besides, the noncoding DNA protects genes by “its own body”. The DNA is put in order in the nucleus of a nonproliferating cell: closer to the nucleus periphery, i.e. in the area where the concentration of mutagens coming from the outside should be the highest, the noncoding DNA is more often situated, but the sections rich in genes are hidden in the center.

During the entire life cycle, the DNA situated in the nucleus of all air-breathing creatures, remains in the flow of mutagens. Some of them, having avoided all barriers set by the cells, burst through into the depth of nucleus and injure the DNA. If mutagens become too numerous, they, according to the authors of the hypothesis, may influence hypothetical molecular sensors, which in their turn mobilize retrotransposons – mobile successions of noncoding section of a genome. As a result, retrotransposons increase in number, and the genome size grows, establishing a correspondence with new needs of the species. If the concentration of mutagens inside the nucleus decreases, the size of a genome will also reduce – its redundant sections will undergo “circumcision”.

If the genome size becomes too big, then mutations would almost not happen and the species evolution practically ceases, its conservation takes place. It is not by accident that gigantic sizes of genomes are typical for “living fossils” – the most ancient animals that have survived to our time.

In the authors’ opinion, the hypothesis reveals a previously unknown protective function of a redundant DNA succession in the genome and explains the C-paradox in a new way. And if the hypothesis is experimentally confirmed, it will be possible to use it for the development of new approaches to genome protection from chemical mutagens, and for overcoming hereditary diseases.