A single protein present in the human brain was found to be the reason why humans are smarter than the rest of the numerous members of the animal kingdom.

Brains come in different sizes and various levels of complexity, especially among vertebrates. People, being the most erect vertebrates, come out as those with the most complex brain structures. With the evolution of man and the rest of the animal world for 350 million years now, it has not been known what exactly makes the human brain stand out from the rest, until now.

In a latest study, scientists from the University of Toronto found that a single molecular event occurring within the human cell may shed light on how we came about as the smartest animal on Earth. According to Professor Benjamin Blencowe at the University's Donnelly Centre, and Banbury Chair in Medical Research, his team of researchers discovered that PTBP1, a small change seen in proteins, stimulates neuron growth, therefore likely causing the brains of mammals to evolve and become the, among other vertebrates, the most complex.

In their study published in the online journal Science, the researchers note an important process called alternative splicing (AS), where the protein building blocks of life are assembled from gene products. During the process, exons or gene fragments are shuffled into proteins of different shapes.

Through AS, more than one protein can be brought about by cells from just one gene. Various proteins present in a cell surpass the number of genes available. The researchers note that the ability of a cell to regulate protein diversity affects the body's ability to perform different functions.

"We wanted to see if AS could drive morphological differences in the brains of different vertebrate species," said Serge Gueroussov, a graduate student working in Blencowe's lab, and the study's lead author. Previously, he also helped identify the protein PTBP1 in a form in mammals. This mammalian form of PTBP1 is shorter, since a tiny fragment gets omitted during AS and the protein doesn't make it through to its final shape.

The prevalence of AS, which is most widespread in the brain, increases as a vertebrate becomes more complex. Although genes are smaller in vertebrates, the proteins are more diverse in mammals than, say in frogs or birds.

In mammalian cells, Gueroussov showed that PTPB1 is also present, only shorter, leading to a series of AS events, affecting protein balance in a way that makes cells neurons. When Geroussov used chicken cells in making shorter PTBP1 similar to the mammalian kind, he saw AS events similar to those found in mammals.

"One interesting implication of our work is that this particular switch between the two versions of PTBP1 could have affected the timing of when neurons are made in the embryo in a way that creates differences in morphological complexity and brain size," said Blencowe.

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