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Comparative Study
. 2016 Jul 29:17:528.
doi: 10.1186/s12864-016-2863-3.

Differences in molecular evolutionary rates among microRNAs in the human and chimpanzee genomes

Gabriel Santpere  1   2 , Maria Lopez-Valenzuela  1 , Natalia Petit-Marty  1 , Arcadi Navarro  3   4   5   6 , Yolanda Espinosa-Parrilla  7   8
Affiliations
Comparative Study

Differences in molecular evolutionary rates among microRNAs in the human and chimpanzee genomes

Gabriel Santpere et al. BMC Genomics. .

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Keywords: Acceleration rates; Divergence; Evolution; Primates; microRNA cluster; microRNAs.

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Figures

Fig. 1
Fig. 1
Workflow diagram of miRNA selection and filtering. The two subsets of miRNAs analyzed in this study are indicated in green boxes. Ali = Alignment
Fig. 2
Fig. 2
Substitution rates of miRNA categories and neutral references
See this image and copyright information in PMC

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References

    1. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999–3004. doi: 10.1073/pnas.0307323101. - DOI - PMC - PubMed
    1. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–269. doi: 10.1038/nrc1840. - DOI - PubMed
    1. Shalgi R, Lieber D, Oren M, Pilpel Y. Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol. 2007;3(7):e131. doi: 10.1371/journal.pcbi.0030131. - DOI - PMC - PubMed
    1. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105. doi: 10.1101/gr.082701.108. - DOI - PMC - PubMed
    1. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet Nature Publishing Group. 2010;11(9):597–610. - PubMed

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