Junk DNA Affects Skeletal Development

Kirill Stasevich, "Science and Life", based on the materials of Science: 'Junk DNA' tells mice—and snakes—how to grow a backbone.

When biologists were just beginning to decipher the DNA sequence, they kept coming across fragments in which no information was recorded.

As we know, all the proteins that make up a living organism are encrypted in DNA with the help of a genetic code; and there are also special sections in the genome that do not encode anything themselves, but affect the activity of coding sequences – roughly speaking, it depends on such regulators whether many molecules of a particular protein appear in the cell. But there are, as we said, fragments of the genome that encode nothing and regulate nothing – they were called junk DNA, which turned out to be more than "meaningful" DNA (and not only in humans, but also in many other species). And for a long time it was believed that this was really garbage accumulated during evolution: pieces of viral nucleic acids that were neutralized in time, so that they fell asleep forever in cell chromosomes, strongly mutated genes that became absolutely useless, etc.

However, recently publications have begun to appear rehabilitating junk DNA. Last year we wrote about the experiments of researchers from the University of Texas Southwestern Medical Center, who found that viral sequences sleeping in the genome help immune cells synthesize antibodies. Last year, the work of the staff of the Karolinska University was published, who claimed on the pages of Nature Communications that junk DNA is necessary for the development of a human embryo. And now another message about the functionality of genomic garbage appeared recently in the Developmental Cell (Aires et. al., Oct4 Is a Key Regulator of Vertical Trunk Length Diversity).

Rita Aires and her colleagues from the Gulbenkian Institute studied mice with non-standard skeletal development. Usually 13 pairs of ribs are formed in these rodents, but some mutants are obtained with 24 pairs – their ribs stretch along the spine right up to the hind legs, and the skeleton of such a mouse resembles the skeleton of a snake (though rather short). It turned out that animals owe such a strange morphology to a mutation that disables the GDF11 gene.

A mouse embryo with an increased number of ribs. Photo from an article in the Developmental Cell.

Normally, GDF11 suppresses the work of another gene – OCT4 – which supports the activity of stem cells and encourages them to turn into other types of cells. That is, due to a mutation in GDF11, OCT4 remains active, which is why stem cells form extra ribs. One would assume that GDF11 is also disabled for snakes, but no – they have it in perfect order. Naturally, there is an assumption that there is still some kind of molecular "player".

Such a "player", as readers might have guessed, turned out to be junk DNA. The OCT4 gene, which stimulates the formation of extra ribs, almost does not differ in snakes, mice and humans, but in the chromosome it is surrounded by non–coding (garbage) areas, which, however, are not completely garbage - they also play a role in inhibiting the work of OCT4. Snakes have non-coding sequences adjacent to OCT4, not the same as others. When snake non–coding DNA was transplanted to mice in the same position – that is, next to OCT4 - then extra ribs appeared in mouse embryos: the gene worked "snake-like", and all because of the so-called junk DNA, which prolonged the work of OCT4. Probably, the GDF11 gene, with which OCT4 disables, works in conjunction with non-coding fragments, and in the case of snakes, these very non-coding fragments have acquired such a form so as not to interfere with the build-up of additional ribs.

As you can see, some parts of junk DNA can play a very important role in determining the anatomy and morphology of the vertebrate body. However, in this case it would be good to create genetically modified snakes, whose non-coding DNA would be edited so that the snake grows shorter. Perhaps such experiments will be possible in the future, but not too soon – now we practically do not know how to manipulate the embryos of reptiles, which go through some stages of development while still in the mother's body, and in a laid egg you can find a snake with 26 pairs of ribs and an already formed head.

But it is possible that similar experiments can be done with other animals that have elongated chests, tails or necks – it can be assumed that non-coding DNA next to OCT4 can affect not only the ribs. Probably, the more we learn about the ways of regulating genetic activity, the more fragments of junk DNA will move from the section of genetic garbage to the section of regulatory sequences.

Portal "Eternal youth" http://vechnayamolodost.ru  23.08.2016