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Evolution of a transcriptional repression domain in an insect Hox protein

Abstract

Homeotic (Hox) genes code for principal transcriptional regulators of animal body regionalization1. The duplication and divergence of Hox genes, changes in their regulation, and changes in the regulation of Hox target genes have all been implicated in the evolution of animal diversity2,3,4. It is not known whether Hox proteins have also acquired new activities during the evolution of specific lineages. Amino-acid sequences outside the DNA-binding homeodomains of Hox orthologues diverge significantly. These sequence differences may be neutral with respect to protein function, or they could be involved in the functional divergence of Hox proteins and the evolutionary diversification of animals. Here, we identify a transcriptional repression domain in the carboxy-terminal region of the Drosophila Ultrabithorax (Ubx) protein. This domain is highly conserved among Ubx orthologues in other insects, but is absent from Ubx in other arthropods and onychophorans. The evolution of this domain may have facilitated the greater morphological diversification of posterior thoracic and anterior abdominal segments characteristic of modern insects.

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Figure 1: Several protein motifs are shared among Ubx orthologues.
Figure 2: Localization of a repression domain in DUbx.
Figure 3: The QA domain is a repression domain.
Figure 4: A repression domain containing poly-alanine evolved in the insect lineage.

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References

  1. McGinnis, W. & Krumlauf, R. Homeobox genes and axial patterning. Cell 68, 283–302 (1992)

    Article  CAS  PubMed  Google Scholar 

  2. Carroll, S. Homeotic genes and the evolution of arthropods and chordates. Nature 376, 479–485 (1995)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Gellon, G. & McGinnis, W. Shaping animal body plans in development and evolution by modulation of Hox expression patterns. BioEssays 20, 116–125 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. Carroll, S. B., Grenier, J. K. & Weatherbee, S. D. From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (Blackwell Science, Malden, Massachusetts, 2001)

    Google Scholar 

  5. McGinnis, N., Kuziora, M. A. & McGinnis, W. Human Hox-4.2 and Drosophila encode similar regulatory specificities in Drosophila embryos and larvae. Cell 63, 969–976 (1990)

    Article  CAS  PubMed  Google Scholar 

  6. Zhao, J. J., Lazzarini, R. A. & Pick, L. The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene. Genes Dev. 7, 343–354 (1993)

    Article  CAS  PubMed  Google Scholar 

  7. Bachiller, D., Macias, A., Dubuoule, D. & Morata, G. Conservation of a functional hierarchy between mammalian and insect Hox/HOM genes. EMBO J. 13, 1930–1941 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zakany, J., Gerard, M., Favier, B., Potter, S. S. & Duboule, D. Functional equivalence and rescue among group 11 Hox gene products in vertebral patterning. Dev. Biol. 176, 325–328 (1996)

    Article  CAS  PubMed  Google Scholar 

  9. Greer, J. M., Puetz, J., Thomas, K. R. & Capecchi, M. R. Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403, 661–665 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Grenier, J. K. & Carroll, S. B. Functional evolution of the Ultrabithorax protein. Proc. Natl Acad. Sci. USA 97, 704–709 (2000)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vachon, G. Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene. Cell 71, 437–450 (1992)

    Article  CAS  PubMed  Google Scholar 

  12. Ronshaugen, M., McGinnis, N. & McGinnis, W. Hox protein mutation and macroevolution of the insect body plan. Nature advance online publication, 6 February 2002 (DOI 10.1038/nature716).

  13. van Dijk, M. & Murre, C. extradenticle raises the DNA binding specificity of homeotic selector gene products. Cell 78, 617–624 (1994)

    Article  CAS  PubMed  Google Scholar 

  14. Chang, C.-P., Shen, W.-F., Rozenfeld, S. & Lawrence, H. J. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes Dev. 9, 663–674 (1995)

    Article  CAS  PubMed  Google Scholar 

  15. Johnson, F. B., Parker, E. & Krasnow, M. A. Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction. Proc. Natl Acad. Sci. USA 92, 739–743 (1995)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Manak, J. R., Mathies, L. D. & Scott, M. P. Regulation of a decapentaplegic midgut enhancer by homeotic proteins. Development 120, 3605–3619 (1994)

    CAS  PubMed  Google Scholar 

  17. Rauskolb, C. & Wieschaus, E. Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins. EMBO J. 13, 3561–3569 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. White, R. A. H., Aspland, S. E., Brookman, J. J., Clayton, L. & Sproat, G. The design and analysis of a homeotic response element. Mech. Dev. 91, 217–226 (2000)

    Article  CAS  PubMed  Google Scholar 

  19. Hanna-Rose, W. & Hansen, U. Active repression mechanisms of eukaryotic transcription repressors. Trends Genet. 12, 229–234 (1996)

    Article  CAS  PubMed  Google Scholar 

  20. Yeung, K., Kim, S. & Reinberg, D. Functional dissection of a human Dr1–DRAP1 repressor complex. Mol. Cell. Biol. 17, 36–45 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Janody, F., Sturny, R., Schaeffer, V., Azou, Y. & Dostatni, N. Two distinct domains of Bicoid mediate its transcriptional downregulation by the Torso pathway. Development 128, 2281–2290 (2001)

    CAS  PubMed  Google Scholar 

  22. Gibson, G. Evolution: Hox genes and the cellared wine principle. Curr. Biol. 10, 452–455 (2000)

    Article  Google Scholar 

  23. Alonso, C. R., Maxton-Kuechenmeister, J. & Akam, M. Evolution of Ftz protein function in insects. Curr. Biol. 11, 1473 (2001)

    Article  CAS  PubMed  Google Scholar 

  24. Löhr, U., Miyuki, Y. & Pick, L. Drosophila fushi tarazu: a gene on the border of homeotic function. Curr. Biol. 11, 1403 (2001)

    Article  PubMed  Google Scholar 

  25. Dearden, P. & Akam, M. Developmental evolution: Axial patterning in insects. Curr. Biol. 9, 591–594 (1999)

    Article  Google Scholar 

  26. Bennett, R. L., Brown, S. J. & Denell, R. E. Molecular and genetic analysis of the Tribolium Ultrabithorax ortholog, Ultrathorax. Dev. Genes Evol. 209, 608–619 (1999)

    Article  CAS  PubMed  Google Scholar 

  27. Castelli-Gair, J., Greig, S., Micklem, G. & Akam, M. Dissecting the temporal requirements for homeotic gene function. Development 120, 1983–1985 (1994)

    CAS  PubMed  Google Scholar 

  28. Brand, A. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993)

    CAS  PubMed  Google Scholar 

  29. Kelsh, R., Weinzierl, R., White, R. & Akam, M. Homeotic gene expression in the locust Schistocerca: An antibody that detects conserved epitopes in Ultrabithorax and abdominal-A genes. Dev. Genet. 15, 19–31 (1994)

    Article  CAS  PubMed  Google Scholar 

  30. Dalton, S. & Treisman, R. Characterization of SAP-1, a protein recruited by serum response factor to the C-fos serum response element. Cell 68, 597 (1992)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank M. Ronshaugen and W. McGinnis for communication of results before publication. We thank D. Lewis for cloning and sequencing JcUbx; M. DeCamillis for providing Tribolium castaneum RNA; R. Mann for providing the Exd expression clone; N. Dostatni and A. Laughon for plasmids; J. Grenier for advice; K. Vorwerk and V. Kassner for technical support; A. Kopp, N. King and J. Grenier for comments; and J. Carroll for help with manuscript preparation. R.G. was supported by a National Institutes of Health predoctoral training grant provided to the Department of Genetics, and S.B.C. is an Investigator of the Howard Hughes Medical Institute.

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Correspondence to Sean B. Carroll.

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Galant, R., Carroll, S. Evolution of a transcriptional repression domain in an insect Hox protein. Nature 415, 910–913 (2002). https://doi.org/10.1038/nature717

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