MicroRNAs (miRNAs) are major factors in the regulation of gene expression. Recent evolutionary studies of miRNAs indicate that important biological innovations, such as the advent of bilateral symmetry and placental reproduction, are accompanied by bursts of miRNA creation which are subsequently conserved via purifying selection. The emergence of eutherian (placental) mammals followed by as much as fifty million years the appearance of the first true mammals in the late Triassic, some 230 million years ago. We have utilized microRNA inventories of eutherian, metatherian (marsupial), monotreme (platypus), and chicken genomes to assemble a minimal microRNA profile of the last common ancestor of all mammals consisting of 171 miRNAs. This profile suggests that the rise of placental reproduction launched a more than three-fold expansion of microRNAs. In addition to expansion of the microRNA repertoire, the conserved microRNAs from five mammalian and one avian genome show evidence for conforming to a canonical phylogenetic history as well as dramatic deviations from the assumptions of molecular clock-like rates and the equality of substitution rates among lineages. We also show that many of these basal mammalian miRNAs are highly expressed in eutherian placenta thus creating an opportunity to gain insight on how microRNAs acquire new targets and new functions.
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