Evolutionary dynamics of microRNA target sites across vertebrate evolution

Autoři: Alfred Simkin aff001;  Rene Geissler aff001;  Alexa B. R. McIntyre aff001;  Andrew Grimson aff001
Působiště autorů: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America aff001;  Department of Biology, Elon University, Elon, North Carolina, United States of America aff002;  Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, United States of America aff003
Vyšlo v časopise: Evolutionary dynamics of microRNA target sites across vertebrate evolution. PLoS Genet 16(2): e1008285. doi:10.1371/journal.pgen.1008285
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008285


MicroRNAs (miRNAs) control the abundance of the majority of the vertebrate transcriptome. The recognition sequences, or target sites, for bilaterian miRNAs are found predominantly in the 3′ untranslated regions (3′UTRs) of mRNAs, and are amongst the most highly conserved motifs within 3′UTRs. However, little is known regarding the evolutionary pressures that lead to loss and gain of such target sites. Here, we quantify the selective pressures that act upon miRNA target sites. Notably, selective pressure extends beyond deeply conserved binding sites to those that have undergone recent substitutions. Our approach reveals that even amongst ancient animal miRNAs, which exert the strongest selective pressures on 3′UTR sequences, there are striking differences in patterns of target site evolution between miRNAs. Considering only ancient animal miRNAs, we find three distinct miRNA groups, each exhibiting characteristic rates of target site gain and loss during mammalian evolution. The first group both loses and gains sites rarely. The second group shows selection only against site loss, with site gains occurring at a neutral rate, whereas the third loses and gains sites at neutral or above expected rates. Furthermore, mutations that alter the strength of existing target sites are disfavored. Applying our approach to individual transcripts reveals variation in the distribution of selective pressure across the transcriptome and between miRNAs, ranging from strong selection acting on a small subset of targets of some miRNAs, to weak selection on many targets for other miRNAs. miR-20 and miR-30, and many other miRNAs, exhibit broad, deeply conserved targeting, while several other comparably ancient miRNAs show a lack of selective constraint, and a small number, including mir-146, exhibit evidence of rapidly evolving target sites. Our approach adds valuable perspective on the evolution of miRNAs and their targets, and can also be applied to characterize other 3′UTR regulatory motifs.

Klíčová slova:

Animal evolution – Animal phylogenetics – MicroRNAs – Natural selection – Nucleotide sequencing – Sequence alignment – Sequence motif analysis – Transcription factors


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