MICRORNAS AND THE EVOLUTION OF VERTEBRATE COMPLEXITY

The notion of complexity is often easy to appreciate but difficult to quantify. Nonetheless, given their almost 3-fold increase in the number of cell types, vertebrates are clearly more complex than invertebrates. It has recently been shown that Osteichthyes are characterized by a dramatic increase in the number of microRNAs (miRNAs), ~22 nucleotide non-coding RNAs that control gene expression by negatively regulating the stability or translation of target mRNAs. Only a handful of new miRNAs evolved at the base of Chordata, but ~73 new miRNA families evolved after the split from other chordates, but before the split between actinopterygian and sarcopterygian fishes. And because one of the roles miRNAs play in development is regulating the balance between cellular proliferation and cellular differentiation, the evolution of new cell types might be controlled, at least to some degree, by the evolution of new miRNAs. Here, we show that of the 36 miRNA families analyzed, 31 are present in lamprey but not in either ascidians or amphioxus (or any other taxon); only two families evolved after the lamprey-human split, and only three evolved before the split. The sheer number of new miRNA families that evolved at the base of Vertebrata represents an unprecedented rate of miRNA acquisition. Indeed, if one assesses the rate of acquisition of all miRNAs families present throughout eutherian mammals per million years from their split from cnidarians up to their split from birds, by far the highest rate of miRNA acquisition occurred at the base of Vertebrata. However, this unique rate of miRNA family acquisition cannot be due to the genome duplication events (GDEs) that occurred early in vertebrate evolution as our data indicate that many of these new miRNA families had evolved before the 2 GDEs. Nonetheless, the genomic position of miRNA paralogues in humans, coupled with gene trees incorporating lamprey orthologues, indicates that both GDEs occurred before the last common ancestor of all living vertebrates. We argue that lying behind the origin of vertebrate complexity might be the dramatic expansion of the non-coding RNA inventory including miRNAs, rather than an increase in the mRNA-encoding inventory due to genomic duplication events.