Introduction and development: The brain size in the Homo genus not only has not increased during the last 150,000 years but has also experienced a slight reduction in the last 35,000 years. This reduction coincides with the generalization of the symbolic culture that was most likely established during the Upper Palaeolithic. Therefore, the cognitive capacities characteristic in the Homo sapiens could be due to structural and functional changes during the brain evolution, rather than an increase of the brain size. Dependence of symbolic culture probably required an increase of the learning and memory skills, thus demanding, at the same time, an improvement of neuroplasticity.
Conclusions: The epsilon3 and epsilon2 alleles of the apolipoprotein E seem to contribute to a better synaptic repairing, in relation to the ancestral epsilon4 allele. Mutation leading to the epsilon3 allele occurred between 220,000 and 150,000 years ago. Its selection and expansion may have continued until a relatively recent period that coincides with the emergence and expansion of the complex symbolic culture. Other factors favouring neuroplasticity, such as certain polymorphisms and the expression increase of certain proteins as reelin, could also have been selected. Emergence of the symbolic behaviour and increase of its deriving technical and social complexity could have made an intense selective pressure leading to a selection of genes that induced an improvement in neuroplasticity. This would constitute an example of gene-culture coevolution.