title: Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.
abstract: BACKGROUND
  The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate.
  
  
  RESULTS
  We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication.
  
  
  CONCLUSIONS
  Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. ferdinand.marletaz@gmail.com.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Marlétaz
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. nacho.maeso@gmail.com.|Present address: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Sevilla, Spain. nacho.maeso@gmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Maeso
authors.affiliation: Department of Biology, University of York, Heslington, York, YO10 5DD, UK. laura.faas@york.ac.uk.
authors.forename: Laura
authors.initials: L
authors.lastname: Faas
authors.affiliation: Department of Biology, University of York, Heslington, York, YO10 5DD, UK. harry.isaacs@york.ac.uk.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Isaacs
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. peter.holland@zoo.ox.ac.uk.
authors.forename: Peter W H
authors.initials: PW
authors.lastname: Holland
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D020440:Gene Duplication; D055785:Gene Knockdown Techniques; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D015398:Signal Transduction; D059467:Transcriptome; D014981:Xenopus / Q000235:genetics* / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D029867:Xenopus Proteins