Functional implications of human-specific changes in great ape microRNAs

Gallego Jiménez, Alicia, 1985-; Melé Messeguer, Marta, 1982-; Balcells, Ingrid; García Ramallo, Eva; Torruella Loran, Ignasi, 1987-; Fernández Bellon, Hugo; Abelló, Teresa; Kondova, Ivanela; Bontrop, Ronald E.; Hvilsom, Christina; Navarro i Cuartiellas, Arcadi, 1969-; Marquès i Bonet, Tomàs, 1975-; Espinosa Parrilla, Yolanda, 1971-

Functional implications of human-specific changes in great ape microRNAs

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dc.contributor.author Gallego Jiménez, Alicia, 1985-ca
dc.contributor.author Melé Messeguer, Marta, 1982-ca
dc.contributor.author Balcells, Ingridca
dc.contributor.author García Ramallo, Evaca
dc.contributor.author Torruella Loran, Ignasi, 1987-ca
dc.contributor.author Fernández Bellon, Hugoca
dc.contributor.author Abelló, Teresaca
dc.contributor.author Kondova, Ivanelaca
dc.contributor.author Bontrop, Ronald E.ca
dc.contributor.author Hvilsom, Christinaca
dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
dc.contributor.author Espinosa Parrilla, Yolanda, 1971-ca
dc.date.accessioned 2016-05-17T16:42:53Z
dc.date.available 2016-05-17T16:42:53Z
dc.date.issued 2016
dc.description.abstract microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra- and inter-species variation in great apes using high-coverage sequenced genomes of 82 individuals including gorillas, orangutans, bonobos, chimpanzees and humans. We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region. We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution. Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR-508-3p and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks. We suggest that the studied molecular changes could have modified crucial microRNA functions shaping phenotypes that, ultimately, became human-specific. Our work provides a frame to study the impact that regulatory changes may have in the recent evolution of our species.ca
dc.description.sponsorship This work was funded by Spanish National Institute for Bioinformatics (www.inab.org); “Ministerio de Ciencia e Innovación de España” [grant numbers BFU2012-38236, BFU2010-18477, BFU2009-06974, CGL2009-09013 and FPI-MINECO to ITL]; “Direcció General de Recerca de la Generalitat de Catalunya” [2009SGR-1101, 2014SGR-866 and SGR2014-1311]; European Union Seventh Framework Programme [grant number PIOF-GA-2009-236836 and PIRSES-GA-2013-612583]; “Ministerio de Educación, Cultura y Deporte de España” [grant FPU-MEC to AG]; FEDER European Regional Development Fund “A way to build Europe”. Three authors of this work were employed by the funding organizations of either the “Parc Zoológic de Barcelona” or the Copenhagen Zoo. The funder “Parc Zoológic de Barcelona” provided support in the form of salaries for authors HFB and TA and the funder Copenhagen Zoo for author CH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.mimetype application/pdfca
dc.identifier.citation Gallego A, Melé M, Balcells I, García-Ramallo E, Torruella-Loran I, Fernández-Bellon H et al. Functional implications of human-specific changes in great ape microRNAs. PLoS One. 2016; 22(11): e0154194. DOI 10.1371/journal.pone.0154194ca
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0154194
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/26286
dc.language.iso engca
dc.publisher Public Library of Scienceca
dc.relation.ispartof PLoS One. 2016; 22(11): e0154194
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-18477
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/236836
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/612583
dc.rights © 2016 Gallego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
dc.subject.other RNAca
dc.subject.other Goril·lesca
dc.title Functional implications of human-specific changes in great ape microRNAsca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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