title: Differences in molecular evolutionary rates among microRNAs in the human and chimpanzee genomes.
abstract: The rise of the primate lineage is accompanied by an outstanding emergence of microRNAs, small non-coding RNAs with a prominent role in gene regulation. In spite of their biological importance little is known about the way in which natural selection has influenced microRNAs in the human lineage. To study the recent evolutionary history of human microRNAs and to analyze the signatures of natural selection in genomic regions harbouring microRNAs we have investigated the nucleotide substitution rates of 1,872 human microRNAs in the human and chimpanzee lineages.
  
  
  
  We produced a depurated set of microRNA alignments of human, chimpanzee and orang-utan orthologs combining BLAT and liftOver and selected 1,214 microRNA precursors presenting optimal secondary structures. We classified microRNAs in categories depending on their genomic organization, duplication status and conservation along evolution. We compared substitution rates of the aligned microRNAs between human and chimpanzee using Tajima's Relative Rate Test taking orang-utan as out-group and found several microRNAs with particularly high substitution rates in either the human or chimpanzee branches. We fitted different models of natural selection on these orthologous microRNA alignments and compared them using a likelihood ratio test that uses ancestral repeats and microRNA flanking regions as neutral sequences. We found that although a large fraction of human microRNAs is highly conserved among the three species studied, significant differences in rates of molecular evolution exist among microRNA categories. Particularly, primate-specific microRNAs, which are enriched in isolated and single copy microRNAs, more than doubled substitution rates of those belonging to older, non primate-specific microRNA families.
  
  
  
  Our results corroborate the remarkable conservation of microRNAs, a proxy of their functional relevance, and indicate that a subset of human microRNAs undergo nucleotide substitutions at higher rates, which may be suggestive of the action of positive selection.
authors.affiliation: Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, (Universitat Pompeu Fabra -CSIC), Barcelona, Catalonia, Spain.|Department of Neurobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Santpere
authors.affiliation: Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, (Universitat Pompeu Fabra -CSIC), Barcelona, Catalonia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Lopez-Valenzuela
authors.affiliation: Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, (Universitat Pompeu Fabra -CSIC), Barcelona, Catalonia, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Petit-Marty
authors.affiliation: Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, (Universitat Pompeu Fabra -CSIC), Barcelona, Catalonia, Spain. arcadi.navarro@upf.edu.|Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. arcadi.navarro@upf.edu.|National Institute for Bioinformatics (INB), Barcelona, Catalonia, Spain. arcadi.navarro@upf.edu.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. arcadi.navarro@upf.edu.
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology, (Universitat Pompeu Fabra -CSIC), Barcelona, Catalonia, Spain. yolespinosa@gmail.com.|School of Medicine, Universidad de Magallanes, Punta Arenas, Chile. yolespinosa@gmail.com.
authors.forename: Yolanda
authors.identifier: 0000-0002-5441-3113
authors.initials: Y
authors.lastname: Espinosa-Parrilla
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D016013:Likelihood Functions; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008957:Models, Genetic; D059645:Mutation Rate; D002679:Pan troglodytes / Q000235:genetics*; D057079:Pongo / Q000235:genetics*; D012641:Selection, Genetic; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: D035683:MicroRNAs
keywords: Acceleration rates; Divergence; Evolution; Primates; microRNA cluster; microRNAs