Alternative Splicing of Single Protein (PTBP1) May Have Led to Remarkable Evolution of Mammalian Brains, the Largest and Most Complex Among Vertebrates

University of Toronto researchers have discovered that a single molecular event in our cells could hold the key to how humans evolved to become the smartest animal on the planet. Benjamin Blencowe, Ph.D., a Professor in the University of Toronto’s Donnelly Centre and Banbury Chair in Medical Research, and his team have uncovered how a small change in a protein called PTBP1 (polypyrimidine-tract-binding protein 1) (image) can spur the creation of neurons – cells that make the brain – that could have fueled the evolution of mammalian brains to become the largest and most complex among vertebrates. The study is published in the August 21, 2015 issue of Science. The article is titled “An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates.” Brain size and complexity vary enormously across vertebrates, but it is not clear how these differences came about. Humans and frogs, for example, have been evolving separately for 350 million years and have very different brain abilities. Yet scientists have shown that they use a remarkably similar repertoire of genes to build organs in the body. So how is it that a similar number of genes, that are also switched on or off in similar ways in diverse vertebrate species, generate a vast range of organ size and complexity? The key lies in the process that Blencowe’s group studies, known as 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 from the same original gene. It’s like LEGO, where some fragments can be missing from the final protein shape.
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