Humans have become the smartest on planet Earth because of a molecular event associated with single protein, researchers have suggested through a new study.
University of Toronto researchers have managed to decode what could have led to development of our super-complex brains and according to them it all boils down to a small change in a protein called PTBP1 that led to a spur in creation of neurons making human brain the most complex among vertebrates.
Published in Journal science, the study attributes the change to a process called alternative splicing (AS), whereby gene products are assembled into proteins, which are the building blocks of life. During AS, gene fragments – called exons – are shuffled to make different protein shapes.
According to researchers, through the process of AS cells make more than one protein from a single gene, so that the total number of different proteins in a cell greatly surpasses the number of available genes. A cell’s ability to regulate protein diversity at any given time reflects its ability to take on different roles in the body.
Benjamin Blencowe, a professor in the University of Toronto’s Donnelly Centre and Banbury Chair in Medical Research, had previously shown that AS prevalence increases with vertebrate complexity. So although the genes that make bodies of vertebrates might be similar, the proteins they give rise to are far more diverse in animals such as mammals, than in birds and frogs. And, the place where AS is more widespread is the brain.
This is what researchers wanted to study. According to Serge Gueroussov, a graduate student in Blencowe’s lab who is the lead author of the study, they wanted to see if AS was responsible for morphological differences in the brains of different vertebrate species.
Gueroussov was one of the researchers who had previously helped identify PTBP1 as a protein capable of taking on another form in mammals, in addition to the one common to all vertebrates. The second form of mammalian PTBP1 is shorter because a small fragment is omitted during AS and does not make it into the final protein shape.
PTBP1 is both a target and major regulator of AS. PTBP1’s job in a cell is to stop it from becoming a neuron by holding off AS of hundreds of other gene products. However, the shorter version of PTBP1 was found to be responsible for a cascade of AS events, that eventually led the cell to become a neuron.
In their study, researchers engineered chicken cells to make the shorter, mammalian-like, PTBP1, and this triggered AS events that are 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,” says Blencowe, who is also a professor in the Department of Molecular Genetics.