Evolutionary History of Chordate PAX Genes: Dynamics of Change in a Complex Gene Family

Paired box (PAX) genes are transcription factors that play important roles in embryonic development. Although the PAX gene family occurs in animals only, it is widely distributed. Among the vertebrates, its 9 genes appear to be the product of complete duplication of an original set of 4 genes, followed by an additional partial duplication. Although some studies of PAX genes have been conducted, no comprehensive survey of these genes across the entire taxonomic unit has yet been attempted. In this study, we conducted a detailed comparison of PAX sequences from 188 chordates, which revealed restricted variation. The absence of PAX4 and PAX8 among some species of reptiles and birds was notable; however, all 9 genes were present in all 74 mammalian genomes investigated. A search for signatures of selection indicated that all genes are subject to purifying selection, with a possible constraint relaxation in PAX4, PAX7, and PAX8. This result indicates asymmetric evolution of PAX family genes, which can be associated with the emergence of adaptive novelties in the chordate evolutionary trajectory.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-09-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0073560PMID 24023886PMCID 3759438
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2013influential reference
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  2013cited by this paper
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  2012cited by this paper
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  2012cited by this paper
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  2011cited by this paper
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  2011cited by this paper
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• Spatiotemporal expression of Pax genes in amphioxus: Insights into Pax-related organogenesis and evolution

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  2010cited by this paper
• Stepwise loss of motilin and its specific receptor genes in rodents.

  2010cited by this paper
• GUIDANCE: a web server for assessing alignment confidence scores

  2010cited by this paper
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  2009cited by this paper
• PhyloBayes 3: a Bayesian software package for phylogenetic reconstruction and molecular dating

  2009cited by this paper
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  2009cited by this paper
• BioMart Central Portal—unified access to biological data

  2009cited by this paper
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  2009cited by this paper
• Preferential subfunctionalization of slow-evolving genes after allopolyploidization in Xenopus laevis

  2008cited by this paper
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• Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after?

  2008cited by this paper
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• The amphioxus genome and the evolution of the chordate karyotype

  2008cited by this paper
• Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage.

  2008cited by this paper
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  2007cited by this paper
• Survey Sequencing and Comparative Analysis of the Elephant Shark (Callorhinchus milii) Genome

  2007cited by this paper
• PAX genes: roles in development, pathophysiology, and cancer.

  2007cited by this paper
• Tunicates and not cephalochordates are the closest living relatives of vertebrates

  2006cited by this paper
• Paleontological evidence to date the tree of life.

  2006cited by this paper
• Getting the Proto-Pax by the Tail

  2006influential reference
• Organisation of the lamprey (Lampetra fluviatilis) embryonic brain: insights from LIM-homeodomain, Pax and hedgehog genes.

  2005cited by this paper
• Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate

  2005cited by this paper
• Comparative genomics of the Hlx homeobox gene and protein: conservation of structure and expression from fish to mammals.

  2005cited by this paper
• The Trichoplax PaxB gene: a putative Proto-PaxA/B/C gene predating the origin of nerve and sensory cells.

  2005cited by this paper
• GeneWise and Genomewise.

  2004cited by this paper
• MUSCLE: multiple sequence alignment with high accuracy and high throughput.

  2004cited by this paper
• The phylogenetic definition of reptilia.

  2004cited by this paper
• A Maximum Likelihood Method for Detecting Functional Divergence at Individual Codon Sites, with Application to Gene Family Evolution

  2004cited by this paper
• Duplication and divergence: the evolution of new genes and old ideas.

  2004cited by this paper
• Pax gene expression in the developing central nervous system of Ciona intestinalis.

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• Conservation of Pax gene expression in ectodermal placodes of the lamprey.

  2002cited by this paper
• Pax6 expression patterns in Lampetra fluviatilis and Scyliorhinus canicula embryos suggest highly conserved roles in the early regionalization of the vertebrate brain.

  2002cited by this paper
• Getting your Pax straight: Pax proteins in development and disease.

  2002influential reference
• Identification and expression of the lamprey Pax6 gene: evolutionary origin of the segmented brain of vertebrates.

  2001cited by this paper
• Statistical methods for detecting molecular adaptation

  2000cited by this paper
• Pax1/Pax9-Related genes in an agnathan vertebrate, Lampetra japonica: expression pattern of LjPax9 implies sequential evolutionary events toward the gnathostome body plan.

  2000cited by this paper
• The evolutionary fate and consequences of duplicate genes.

  2000cited by this paper
• AmphiPax3/7, an amphioxus paired box gene: insights into chordate myogenesis, neurogenesis, and the possible evolutionary precursor of definitive vertebrate neural crest

  1999cited by this paper
• Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.

  1998cited by this paper
• Pax-6 origins – implications from the structure of two coral Pax genes

  1998cited by this paper
• Evolution of functional diversification of the paired box (Pax) DNA-binding domains.

  1997cited by this paper
• Hox genes and chordate evolution.

  1996cited by this paper
• The timing of early developmental events in Xenopus

  1985cited by this paper
• Evolution by Gene Duplication

  1970cited by this paper

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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
• Conservatism and variability of gene expression profiles among homeologous transcription factors in Xenopus laevis.

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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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