Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence

Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development. In zebrafish, following a postulated whole-genome duplication event in an ancestral teleost, dupli...

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Main Authors:	Kleinjan, Dirk A, Bancewicz, Ruth M, Gautier, Philippe, Dahm, Ralf, Schonthaler, Helia B, Damante, Giuseppe, Seawright, Anne, Hever, Ann M, Yeyati, Patricia L, van Heyningen, Veronica, Coutinho, Pedro
Format:	Online
Language:	English
Published:	Public Library of Science 2008
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242813/

id	pubmed-2242813
recordtype	oai_dc
spelling	pubmed-22428132008-02-15 Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence Kleinjan, Dirk A Bancewicz, Ruth M Gautier, Philippe Dahm, Ralf Schonthaler, Helia B Damante, Giuseppe Seawright, Anne Hever, Ann M Yeyati, Patricia L van Heyningen, Veronica Coutinho, Pedro Research Article Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development. In zebrafish, following a postulated whole-genome duplication event in an ancestral teleost, duplicates pax6a and pax6b jointly fulfill these roles. Mapping of the homozygously viable eye mutant sunrise identified a homeodomain missense change in pax6b, leading to loss of target binding. The mild phenotype emphasizes role-sharing between the co-orthologues. Meticulous mapping of isolated BACs identified perturbed synteny relationships around the duplicates. This highlights the functional conservation of pax6 downstream (3′) control sequences, which in most vertebrates reside within the introns of a ubiquitously expressed neighbour gene, ELP4, whose pax6a-linked exons have been lost in zebrafish. Reporter transgenic studies in both mouse and zebrafish, combined with analysis of vertebrate sequence conservation, reveal loss and retention of specific cis-regulatory elements, correlating strongly with the diverged expression of co-orthologues, and providing clear evidence for evolution by subfunctionalization. Public Library of Science 2008-02-15 /pmc/articles/PMC2242813/ /pubmed/18282108 http://dx.doi.org/10.1371/journal.pgen.0040029 Text en © 2008 Kleinjan et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kleinjan, Dirk A Bancewicz, Ruth M Gautier, Philippe Dahm, Ralf Schonthaler, Helia B Damante, Giuseppe Seawright, Anne Hever, Ann M Yeyati, Patricia L van Heyningen, Veronica Coutinho, Pedro
spellingShingle	Kleinjan, Dirk A Bancewicz, Ruth M Gautier, Philippe Dahm, Ralf Schonthaler, Helia B Damante, Giuseppe Seawright, Anne Hever, Ann M Yeyati, Patricia L van Heyningen, Veronica Coutinho, Pedro Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
author_facet	Kleinjan, Dirk A Bancewicz, Ruth M Gautier, Philippe Dahm, Ralf Schonthaler, Helia B Damante, Giuseppe Seawright, Anne Hever, Ann M Yeyati, Patricia L van Heyningen, Veronica Coutinho, Pedro
author_sort	Kleinjan, Dirk A
title	Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
title_short	Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
title_full	Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
title_fullStr	Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
title_full_unstemmed	Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
title_sort	subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence
description	Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development. In zebrafish, following a postulated whole-genome duplication event in an ancestral teleost, duplicates pax6a and pax6b jointly fulfill these roles. Mapping of the homozygously viable eye mutant sunrise identified a homeodomain missense change in pax6b, leading to loss of target binding. The mild phenotype emphasizes role-sharing between the co-orthologues. Meticulous mapping of isolated BACs identified perturbed synteny relationships around the duplicates. This highlights the functional conservation of pax6 downstream (3′) control sequences, which in most vertebrates reside within the introns of a ubiquitously expressed neighbour gene, ELP4, whose pax6a-linked exons have been lost in zebrafish. Reporter transgenic studies in both mouse and zebrafish, combined with analysis of vertebrate sequence conservation, reveal loss and retention of specific cis-regulatory elements, correlating strongly with the diverged expression of co-orthologues, and providing clear evidence for evolution by subfunctionalization.
publisher	Public Library of Science
publishDate	2008
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242813/
_version_	1611439015588790272

Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence

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