Left-handed people are three times more likely than right-handed people to have genetic variations in a part of the DNA responsible for making microtubules, structures that give shape to neurons. These non-hereditary mutations are very rare (they affect one in every thousand left-handers), but they point to these structures as determinants in the choice of the dominant hand.
The key to the finding, carried out on a sample of more than 350,000 British citizens, and published this Tuesday in Nature Communications, is that these mutations are in an area of the DNA in which they cause a gene, called TUBB4B, to produce proteins different from those usual. That is, they alter the composition of microtubules, and these alterations make it more likely that a person will be left-handed.
“Although the variants are only found in less than 1 in every 1,000 left-handed people, the finding is important because it implicates TUBB4B in the development of cerebral asymmetry in other people,” Clyde Francks, a neurobiologist at the Max Planck Institute for Neuropathy, explains to La Vanguardia. Psycholinguistics, in the Netherlands, who led the study. What the expert means by this is that the gene in question is key in the development of the brain of the entire population, both right-handed and left-handed.
The brain consists of two somewhat different (asymmetric) halves, each of them specialized in different tasks. For the majority of the population, for example, the dominant hand is governed by the left hemisphere of the brain, and that is why 90% of people are right-handed. In left-handed people, it is the right half of the organ that is responsible for managing the dominant hand, the left.
The reason for this difference, however, is one of the mysteries that the field has not yet been able to solve. The current work rules out that left-handed people generally have genetic mutations that right-handed people do not have. Previous work had also ruled out that environmental factors (such as having twins, having been breastfed or having had medical problems during childbirth) explained the phenomenon at the population level.
“We believe that in most cases it occurs simply due to random variations during the development of the embryonic brain,” such as changes in the concentrations of certain molecules, Franck points out, which end up modifying the anatomy of the hemispheres. Regardless of the underlying cause—random, genetic, or environmental—research points to microtubules as responsible for the brain asymmetry that ends up making a person right- or left-handed.
Previous research had already found that some left-handed people had relatively frequent mutations in genes involved in the formation of microtubules. The effects of these variations were, however, "very small", according to Francks, "they affect, for example, how active a gene is within a certain tissue," he details. They had no consequences on protein production, which is just the type of mutation his team has found.
The fact that the current work coincides with previous ones in the type of genes affected, “is a nice convergence of evidence,” the expert values. “It suggests that microtubules are involved in forming normal brain asymmetries.”
The researcher points out that, probably, the genome is encoded so that the asymmetry of the brain is such that human beings are right-handed, and that microtubules have a lot to say there, either because of the shape they give to the cell, or because of how they move it. This is, in fact, the next step that they want to evaluate in the laboratory.
“We want to investigate the role of microtubules in the embryonic development of brain asymmetry,” he explains, pointing to mouse embryos as candidates for the study. As so many times in science, a work begun to answer a question whose mystery persists—what makes 10% of the population left-handed?—gives rise to new questions.
