MicroRNAs as prime players in a combinatorial view of evolution.

MicroRNA-mediated gene regulation allows the establishment of complex circuitries acting in many different phases of development and differentiation. MicroRNA genes and their target sites are under Darwinian selection and the idea that microRNAs can act as prime players in determining species identity has been recently speculated. By studying the 3'-untranslated regions (UTRs) of orthologous neuronal genes, we found that, at variance with house-keeping genes, the density of miRNA target sites involved in complex cell networks increased from invertebrates to human, paralleling the increase in species complexity. This suggests that genes contributing to complex cellular functions had a selective advantage for acquiring and potentiate miRNA-mediated regulation.