Human brain evolution: searching the genetic basis underlying our unique cognitive capacities

LUCÍA F. FRANCHINI

Huerta Grande

Conferencia; Simposio: Brain Development and Evolution; 2011

Sociedad Argentina de Investigación en Neurociencias

It has been hypothesized that the evolution of the unique human cognitive capacities is due to the acquisition of new temporal and spatial expression patterns of preexisting genes rather than changes in the protein-coding sequences. Using a combination of bioinformatics and functional studies including the generation of transgenic zebrafish and mice we are investigating differences in gene regulation which may have contributed to the evolution of the human brain. I will present here our results involving the functional characterization of regulatory elements of two key brain development genes that evolved faster in the human lineage. We have uncovered a novel enhancer of DLL1, a gene involved in the proliferation/differentiation switch of neuronal precursors that positively evolved in primates. We have found that the primate-specific changes are crucial for this regulatory element function during brain development. In addition, we are functionally characterizing the largest cluster of the most rapidly evolving human elements yet identified (termed [HARs]) located within 648 kb of the NPAS3 gene. We tested the ability of NPAS3-HARs to function as developmental enhancers. Our results indicated that the regulation of NPAS3 and DLL1 has been shaped during human evolution, suggesting that changes in its expression pattern could have been crucial for the evolution of the human brain.