Inferring the evolutionary history of primate microRNA binding sites: Overcoming motif counting biases

Alfred T. Simkin, Jeffrey A. Bailey, Fen Biao Gao, Jeffrey Jensen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The first microRNAs (miRNAs) were identified as essential, conserved regulators of gene expression, targeting the same genes across nearly all bilaterians. However, there are also prominent examples of conserved miRNAs whose functions appear to have shifted dramatically, sometimes over very brief periods of evolutionary time. To determine whether the functions of conserved miRNAs are stable or dynamic over evolutionary time scales, we have here defined the neutral turnover rates of short sequence motifs in predicted primate 3'-UTRs. We find that commonly used approaches to quantify motif turnover rates, which use a presence/absence scoring in extant lineages to infer ancestral states, are inherently biased to infer the accumulation of new motifs, leading to the false inference of continually increasing regulatory complexity over time. Using a maximum likelihood approach to reconstruct individual ancestral nucleotides, we observe that binding sites of conserved miRNAs in fact have roughly equal numbers of gain and loss events relative to ancestral states and turnover extremely slowly relative to nearly identical permutations of the same motif. Contrary to case studies showing examples of functional turnover, our systematic study of miRNA binding sites suggests that in primates, the regulatory roles of conserved miRNAs are strongly conserved. Our revised methodology may be used to quantify the mechanism by which regulatory networks evolve.

Original languageEnglish (US)
Pages (from-to)1894-1901
Number of pages8
JournalMolecular Biology and Evolution
Volume31
Issue number7
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

MicroRNAs
microRNA
primate
Primates
binding sites
turnover
History
Binding Sites
history
targeting
gene expression
Gene Targeting
3' Untranslated Regions
gene targeting
3' untranslated regions
Regulator Genes
regulator genes
timescale
methodology
gene

Keywords

  • miRNA evolution
  • molecular evolution
  • molecular phylogeny
  • motif turnover
  • parsimony
  • regulatory network

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Medicine(all)

Cite this

Inferring the evolutionary history of primate microRNA binding sites : Overcoming motif counting biases. / Simkin, Alfred T.; Bailey, Jeffrey A.; Gao, Fen Biao; Jensen, Jeffrey.

In: Molecular Biology and Evolution, Vol. 31, No. 7, 2014, p. 1894-1901.

Research output: Contribution to journalArticle

Simkin, Alfred T. ; Bailey, Jeffrey A. ; Gao, Fen Biao ; Jensen, Jeffrey. / Inferring the evolutionary history of primate microRNA binding sites : Overcoming motif counting biases. In: Molecular Biology and Evolution. 2014 ; Vol. 31, No. 7. pp. 1894-1901.
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