Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals

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• dc.contributor.author Maeso, Ignacioca
• dc.contributor.author Dunwell, Thomas L.ca
• dc.contributor.author Wyatt, Christopher Douglas Robert, 1988-ca
• dc.contributor.author Marlétaz, Ferdinandca
• dc.contributor.author Vető, Borbálaca
• dc.contributor.author Bernal, Juan A.ca
• dc.contributor.author Quah, Shanca
• dc.contributor.author Irimia Martínez, Manuelca
• dc.contributor.author Holland, Peter W. H.ca
• dc.date.accessioned 2016-11-08T16:41:09Z
• dc.date.available 2016-11-08T16:41:09Z
• dc.date.issued 2016ca
• dc.description.abstract BACKGROUND: A central goal of evolutionary biology is to link genomic change to phenotypic evolution. The origin of new transcription factors is a special case of genomic evolution since it brings opportunities for novel regulatory interactions and potentially the emergence of new biological properties. RESULTS: We demonstrate that a group of four homeobox gene families (Argfx, Leutx, Dprx, Tprx), plus a gene newly described here (Pargfx), arose by tandem gene duplication from the retinal-expressed Crx gene, followed by asymmetric sequence evolution. We show these genes arose as part of repeated gene gain and loss events on a dynamic chromosomal region in the stem lineage of placental mammals, on the forerunner of human chromosome 19. The human orthologues of these genes are expressed specifically in early embryo totipotent cells, peaking from 8-cell to morula, prior to cell fate restrictions; cow orthologues have similar expression. To examine biological roles, we used ectopic gene expression in cultured human cells followed by high-throughput RNA-seq and uncovered extensive transcriptional remodelling driven by three of the genes. Comparison to transcriptional profiles of early human embryos suggest roles in activating and repressing a set of developmentally-important genes that spike at 8-cell to morula, rather than a general role in genome activation. CONCLUSIONS: We conclude that a dynamic chromosome region spawned a set of evolutionarily new homeobox genes, the ETCHbox genes, specifically in eutherian mammals. After these genes diverged from the parental Crx gene, we argue they were recruited for roles in the preimplantation embryo including activation of genes at the 8-cell stage and repression after morula. We propose these new homeobox gene roles permitted fine-tuning of cell fate decisions necessary for specification and function of embryonic and extra-embryonic tissues utilised in mammalian development and pregnancy.
• dc.description.sponsorship This work was supported primarily by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013 ERC grant 268513) to PWHH. In addition, support was provided by the Spanish Ministry of Economy and Competitiveness (BFU2014-55076-P) to MI and a fellowship from ‘la Caixa’-Severo Ochoa to CDRW
• dc.format.mimetype application/pdfca
• dc.identifier.citation Maeso I, Dunwell T, Wyatt C, Marlétaz F, Vető B, Bernal J et al. Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals. BMC Biology. 2016;14:45. DOI: 10.1186/s12915-016-0267-0ca
• dc.identifier.doi http://dx.doi.org/10.1186/s12915-016-0267-0
• dc.identifier.issn 1741-7007ca
• dc.identifier.uri http://hdl.handle.net/10230/27468
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof BMC Biology. 2016;14:45
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/268513ca
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55076-P
• dc.rights © 2016 Maeso et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Tandem duplication
• dc.subject.keyword Asymmetric evolution
• dc.subject.keyword Embryo
• dc.subject.keyword Placental
• dc.subject.keyword Homeodomain
• dc.subject.keyword PRD
• dc.title Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammalsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca