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The intelligence leaps

Strips of mobile DNA regulate the differentiation of nerve cells

Some biological clues have appeared towards understanding why the same painting or an identical situation makes a person laugh, leads another to tears and leaves a third completely indifferent. The differences in perception, the ability to react with greater or lesser rapidity to being cut off in the traffic or even of intelligence more or less ascertained, are rooted in genetics – specifically in the consequences of the movements of sequences of DNA capable of jumping from one point of the genome to another, the so-called retrotransposons.

Depending upon where they are stationed, these mobile elements can activate or silence genes responsible for the differentiation of neuron cells, precursors of neurons. Thus they form a mosaic of neurons, which translate into a greater or lesser ability towards being emotionally affected by a picture or of figuring out a physics problem. Carried out by a team from the Salk Institute, in the United States, this study was able to count upon two Brazilian biologists, Alysson Muotri and Maria Carolina Marchetto, and opens up the prospective of deepening the research into illnesses such as autism and schizophrenia, which could result, at first glance, from the positions in which the retrotransposons situate themselves. “Our hypothesis is that the leaps of the retrotransposons in adult nerve cells can be contributing to a generating diversity of the brain neurons, conferring adaptability and contributing to each individual having a unique brain”, comments Maria Carolina.

Published in the 16th of May edition of the magazine Nature, the work has other merits. In the first place it confirms the value of the jumping genes as the controlling elements of the genome. Some sixty years ago the American geneticist Barbara McClintock discovered the jumping genes and launched the idea of studying the origins of the variations of the color of corn, but was forgotten about for almost forty years until she won the Nobel Prize for Medicine in 1983. Even though other studies had shown this ability of interfering in the characteristics of a human being, the retrotransposons remained somewhat unseemly: it had been suspected that they could be selfish and parasitic genes, thus called because they move themselves with the exclusive objective of self-reproduction, without any contribution to the organism – a hypothesis sustained by the fact of their movements previously having been observed in germinative cells (ovules and spermatozoids) and in tumors, but never, up until now, in somatic cells, especially in the brain.

As well as this, this study presents indications of how one of the types of retrotransposons,  the Line-1 or  L1, which occupies around 20% of the genome of mammals, works. Other ideas gain new adaptations. “It had been thought that the genetic regions that contain the genes linked to the nervous system had been protected against these mobile elements of the DNA”, comments Marie-Anne van Sluys, a specialist in the mobile elements who works at the Biosciences Institute of the University of Sao Paulo (USP). But the L-1s create copies of themselves even if they fit exactly into the DNA regions richest in genes responsible for the formation of nerve cells, favored for a moment in which the genes are being copied and the DNA finds itself only slightly coiled up.

But why do the L1s look for exactly the genes whose activity determines the future of the nerve cells? “Apparently”, comments Carlos Menck, a professor at the Biomedical Sciences Institute of USP who supervised the doctorate students Muotri and Maria Carolina, “the L1s appear specifically to modulate the expression of genes of differentiated cells”. They would not be the first: other studies have already shown that other types of mobile elements regulate the expression of genes during the formation of the embryo. According to professor Menck, these studies could constitute indications of a process that is not necessarily chance, but of some mechanism that activates the retrotransposons in a specific moment.

The work of the two Brazilians at the Fred Gage laboratory of the Salk Institute has shown that the L1s act more freely when the activity of the genes known as Sox2 is lower. Thus, the Sox2 might not only be casual blockers of these retrotransposons, but intermediary actors of this mechanism of activation or blockage of the genes of the neurons, which would result in neurons that would more or less make connections among themselves, leading, in a wider plan, to animals or human beings with distinctive behavior – more aggressive or more pacific or, in a general manner, capable of responding in a different manner to a stimulus.

Such conclusions resulted in tests done on transgenic mice, which had carried copies of a human active L1, marked with a green florescent protein. Thus, the cells in whose DNA they implant themselves remain green. When the experiment was completed, “only the brain cells and the germinative cells remained green”, says Muotri. Not one of the animals had the same green cells – an indication that the interaction with the environment and a good dose of chance are still decisive for determining the future of the neurons. This is a game of uncertain results: “Even genetically identical animals,” he says, “have different brains”.