Genetic Basis of Humanness: Determining the Role of Hominoid-Specific and Human-Specific Gene Duplications during Brain Development
Franck Polleux, Dorris Neuroscience Center, The Scripps Research Institute
What makes us humans? In particular, during evolution, what genetic mechanisms have allowed the emergence of specific traits characterizing the human brain? These questions represent some of the most challenging problems remaining in biology and have fascinated generations of philosophers, sociologists, anthropologists, geneticists, neuroscientists and evolutionary biologists. The identification of the genetic mechanisms underlying human-specific brain development during evolution will transform our ability to decipher the pathophysiological mechanisms underlying neurodevelopment disorders affecting human-specific cognitive abilities such as autism or schizophrenia.
Gene duplication is one of the major driving force driving evolution and speciation (Ohno, 1970). Recent breakthroughs in evolutionary genomics show that a burst of gene duplications occurred in the human lineage during its separation from non-human primates approximately 6 million years ago (Bailey et al., 2002; Fortna et al., 2004; Marques-Bonet et al., 2009). The long-term scientific goal of our project is aimed at determining the role of hominoid- and human-specific gene duplications during brain development and evolution. We have obtained recent evidence showing that one of these human-specific gene duplication affecting a gene called SRGAP2 play a key role during synaptic development and controls the total number of synaptic connections established by cortical neurons. These results open the first time the possibility of identifying human-specific modifiers of neuronal connectivity that have played a key role during human brain evolution.
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