Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence
Abstract
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 (39) 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 coorthologues, and providing clear evidence for evolution by subfunctionalization.
- Authors:
-
- Western General Hospital, Edinburgh, Scotland (United Kingdom). Medical Research Council (MRC) Human Genetics Unit
- Max-Planck Inst. for Developmental Biology, Tubingen (Germany). Dept. of Genetics
- Univ. of Udine (Italy). Dept. of Science and Biomedical Technology
- Publication Date:
- Research Org.:
- Western General Hospital, Edinburgh, Scotland (United Kingdom). Medical Research Council (MRC) Human Genetics Unit
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1627269
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Genetics
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 2; Journal ID: ISSN 1553-7404
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Genetics & Heredity
Citation Formats
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, and Coutinho, Pedro. Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence. United States: N. p., 2008.
Web. doi:10.1371/journal.pgen.0040029.
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. United States. https://doi.org/10.1371/journal.pgen.0040029
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, and Coutinho, Pedro. Fri .
"Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence". United States. https://doi.org/10.1371/journal.pgen.0040029. https://www.osti.gov/servlets/purl/1627269.
@article{osti_1627269,
title = {Subfunctionalization of Duplicated Zebrafish pax6 Genes by cis-Regulatory Divergence},
author = {Kleinjan, Dirk A. and Bancewicz, Ruth M. and Gautier, Philippe and Dahm, Ralf and Schonthaler, Helia B. and Damante, Giuseppe and Seawright, Anne and Hever, Ann M. and Yeyati, Patricia L. and van Heyningen, Veronica and Coutinho, Pedro},
abstractNote = {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 (39) 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 coorthologues, and providing clear evidence for evolution by subfunctionalization.},
doi = {10.1371/journal.pgen.0040029},
journal = {PLoS Genetics},
number = 2,
volume = 4,
place = {United States},
year = {Fri Feb 15 00:00:00 EST 2008},
month = {Fri Feb 15 00:00:00 EST 2008}
}
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