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Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs

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Abstract

T-box genes encode a family of DNA-binding transcription factors implicated in numerous developmental processes in all metazoans. The Tbx2/3/4/5 subfamily genes are especially interesting because of their key roles in the evolution of vertebrate appendages, eyes, and the heart, and, like the Hox genes, the longevity of their chromosomal linkage. A BAC library derived from the single male amphioxus (Branchiostoma floridae) used to sequence the amphioxus genome was screened for AmphiTbx2/3 and AmphiTbx4/5, yielding two independent clones containing both genes. Using comparative expression, genomic linkage, and phylogenetic analyses, we have reconstructed the evolutionary histories of these members of the T-box gene family. We find that the Tbx2–Tbx4 and Tbx3–Tbx5 gene pairs have maintained tight linkage in most animal lineages since their birth by tandem duplication, long before the divergence of protostomes and deuterostomes (e.g., arthropods and vertebrates) at least 600 million years ago, and possibly before the divergence of poriferans and cnidarians (e.g., sponges and jellyfish). Interestingly, we find that the gene linkage detected in all vertebrate genomes has been maintained in the primitively appendage-lacking, basal chordate, amphioxus. Although all four genes have been involved in the evolution of developmental programs regulating paired fin and (later) limb outgrowth and patterning, and most are also implicated in eye and heart development, linkage maintenance—often considered due to regulatory constraints imposed by limb, eye, and/or heart associated gene expression—is undoubtedly a consequence of other, much more ancient functional constraints.

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Author notes

  1. Amy C. Horton

    Present address: Genome Sequencing Center, Department of Genetics, Washington University in St. Louis School of Medicine, 4444 Forest Park Ave., St. Louis, MO, 63108, USA

  2. Carolina Minguillon

    Present address: CSIC–Institut de Biologia Molecular de Barcelona, Parc Cientific de Barcelona, C/ Josep Samitier 1-5, 08028, Barcelona, Spain

  3. Jeremy J. Gibson-Brown

    Present address: Institute for Evolutionary Discovery, 909 Hiawatha Drive, Mount Pleasant, MI, 48858, USA

Authors and Affiliations

  1. Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO, 63130, USA

    Amy C. Horton, Navin R. Mahadevan & Jeremy J. Gibson-Brown

  2. Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Carolina Minguillon & Malcolm P. Logan

  3. BACPAC Resources, Children’s Hospital Oakland Research Institute, 747 52nd Street, Oakland, CA, 94609, USA

    Kazutoyo Osoegawa & Pieter J. de Jong

  4. Department of Computational Genomics, Joint Genome Institute of the US Department of Energy, 2800 Mitchell Avenue, Walnut Creek, CA, 94598, USA

    Daniel S. Rokhsar

  5. Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL, 60637, USA

    Ilya Ruvinsky

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Correspondence to Jeremy J. Gibson-Brown.

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Communicated by N. Satoh

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Supplementary Fig. 1

Amino acid alignment used for the phylogenetic analysis depicted in Figure 1 (PDF 45.0 KB)

Supplementary Table 1

Amino acid coordinates of coding exons. Exon numbering as in Wattler et al. (1998) with subsequent exons numbered serially (DOC 37.5 KB)

Supplementary Table 2

Sizes of introns within coding regions. Intron numbering as in Wattler et al. (1998) with the addition of intron 0, between 5′ UTR and first coding exon, and introns 5, 6, and 7. Large (>5 kb) introns in bold type (DOC 44.0 KB)

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Horton, A.C., Mahadevan, N.R., Minguillon, C. et al. Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs. Dev Genes Evol 218, 613–628 (2008). https://doi.org/10.1007/s00427-008-0249-5

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