Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution

<p>ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, <em>Cone-rod homeobox</em> (<em>CRX</em>). While expression and function of <em>CRX</e...

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Main Authors: Royall, A, Frankenberg, S, Pask, A, Holland, P
Format: Journal article
Published: Royal Society 2019
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author Royall, A
Frankenberg, S
Pask, A
Holland, P
author_facet Royall, A
Frankenberg, S
Pask, A
Holland, P
author_sort Royall, A
collection OXFORD
description <p>ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, <em>Cone-rod homeobox</em> (<em>CRX</em>). While expression and function of <em>CRX</em> are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles between <em>CRX</em> and ETCHbox genes. To resolve between these hypotheses, we compared expression, sequence and inferred function between <em>CRX</em> of metatherian (marsupial) mammals and ETCHbox genes of eutherians. We find the metatherian <em>CRX</em> homeobox gene is expressed in early embryos and in eyes, unlike eutherian <em>CRX</em>, and distinct amino acid substitutions were fixed in the metatherian and eutherian evolutionary lineages consistent with altered transcription factor specificity. We find that metatherian <em>CRX</em> is capable of regulating embryonically expressed genes in cultured cells in a comparable way to eutherian ETCHbox. The data are consistent with <em>CRX</em> having a dual role in eyes and embryos of metatherians, providing an early embryonic function comparable to that of eutherian ETCHbox genes; we propose that subfunctionalization of pleiotropic functions occurred after gene duplication along the placental lineage, followed by functional elaboration.</p>
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spelling oxford-uuid:2faf675a-2901-4281-83e0-47e01cd30e112022-03-26T12:56:48ZOf eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolutionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2faf675a-2901-4281-83e0-47e01cd30e11Symplectic Elements at OxfordRoyal Society2019Royall, AFrankenberg, SPask, AHolland, P<p>ETCHbox genes are fast-evolving homeobox genes present only in eutherian (placental) mammals which originated by duplication and divergence from a conserved homeobox gene, <em>Cone-rod homeobox</em> (<em>CRX</em>). While expression and function of <em>CRX</em> are restricted to the retina in eutherian mammals, ETCHbox gene expression is specific to preimplantation embryos. This dramatic difference could reflect the acquisition of new functions by duplicated genes or subfunctionalization of pleiotropic roles between <em>CRX</em> and ETCHbox genes. To resolve between these hypotheses, we compared expression, sequence and inferred function between <em>CRX</em> of metatherian (marsupial) mammals and ETCHbox genes of eutherians. We find the metatherian <em>CRX</em> homeobox gene is expressed in early embryos and in eyes, unlike eutherian <em>CRX</em>, and distinct amino acid substitutions were fixed in the metatherian and eutherian evolutionary lineages consistent with altered transcription factor specificity. We find that metatherian <em>CRX</em> is capable of regulating embryonically expressed genes in cultured cells in a comparable way to eutherian ETCHbox. The data are consistent with <em>CRX</em> having a dual role in eyes and embryos of metatherians, providing an early embryonic function comparable to that of eutherian ETCHbox genes; we propose that subfunctionalization of pleiotropic functions occurred after gene duplication along the placental lineage, followed by functional elaboration.</p>
spellingShingle Royall, A
Frankenberg, S
Pask, A
Holland, P
Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title_full Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title_fullStr Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title_full_unstemmed Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title_short Of eyes and embryos: subfunctionalisation of the CRX homeobox gene in mammalian evolution
title_sort of eyes and embryos subfunctionalisation of the crx homeobox gene in mammalian evolution
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AT frankenbergs ofeyesandembryossubfunctionalisationofthecrxhomeoboxgeneinmammalianevolution
AT paska ofeyesandembryossubfunctionalisationofthecrxhomeoboxgeneinmammalianevolution
AT hollandp ofeyesandembryossubfunctionalisationofthecrxhomeoboxgeneinmammalianevolution