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Hox protein mutation and macroevolution of the insect body plan

Abstract

A fascinating question in biology is how molecular changes in developmental pathways lead to macroevolutionary changes in morphology. Mutations in homeotic (Hox) genes have long been suggested as potential causes of morphological evolution1,2, and there is abundant evidence that some changes in Hox expression patterns correlate with transitions in animal axial pattern3. A major morphological transition in metazoans occurred about 400 million years ago, when six-legged insects diverged from crustacean-like arthropod ancestors with multiple limbs4,5,6,7. In Drosophila melanogaster and other insects, the Ultrabithorax (Ubx) and abdominal A (AbdA, also abd-A) Hox proteins are expressed largely in the abdominal segments, where they can suppress thoracic leg development during embryogenesis3. In a branchiopod crustacean, Ubx/AbdA proteins are expressed in both thorax and abdomen, including the limb primordia, but do not repress limbs8,9,10,11. Previous studies led us to propose that gain and loss of transcriptional activation and repression functions in Hox proteins was a plausible mechanism to diversify morphology during animal evolution12. Here we show that naturally selected alteration of the Ubx protein is linked to the evolutionary transition to hexapod limb pattern.

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Figure 1: Evolution of trunk Hox gene expression patterns and sequence comparison of arthropod Ubx proteins.
Figure 2: Comparison of the effects of ectopic Artemia franciscana (Af) Ubx and Drosophila melanogaster (Dm) Ubx proteins on Drosophila morphology and Ubx target genes.
Figure 3: Repression of thoracic limbs by Artemia/Drosophila Ubx hybrid proteins.
Figure 4: The evolution of Ubx and Antp protein sequence in insects and other arthropods.

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References

  1. Goldschmidt, R. The Material Basis of Evolution (Yale Univ. Press, New Haven, Connecticut, 1940)

    Google Scholar 

  2. Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature 276, 565–570 (1978)

    Article  CAS  ADS  Google Scholar 

  3. Carroll, S. B., Grenier, J. K. & Weatherbee, S. D. From DNA to Diversity (Blackwell Science, London, 2001)

    Google Scholar 

  4. Boore, J. L., Collins, T. M., Stanton, D., Daehler, L. L. & Brown, W. M. Deducing the pattern of arthropod phylogeny from mitochondrial DNA rearrangements. Nature 376, 163–165 (1995)

    Article  CAS  ADS  Google Scholar 

  5. Friedrich, M. & Tautz, D. Ribosomal DNA phylogeny of the major extant arthropod classes and the evolution of myriapods. Nature 376, 165–167 (1995)

    Article  CAS  ADS  Google Scholar 

  6. Aguinaldo, A. et al. Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 387, 489–493 (1997)

    Article  CAS  Google Scholar 

  7. Regier, J. C. & Shultz, J. W. Molecular phylogeny of the major arthropod groups indicates polyphyly of crustaceans and a new hypothesis for the origin of hexapods. Mol. Biol. Evol. 14, 902–913 (1997)

    Article  CAS  Google Scholar 

  8. Averof, M. & Akam, M. Hox genes and the diversification of insect and crustacean body plans. Nature 376, 420–423 (1995)

    Article  CAS  ADS  Google Scholar 

  9. Averof, M. & Patel, N. Crustacean appendage evolution associated with changes in Hox gene expression. Nature 388, 682–686 (1997)

    Article  CAS  ADS  Google Scholar 

  10. Panganiban, G., Sebring, A., Nagy, L. & Carroll, S. The development of crustacean limbs and the evolution of arthropods. Science 270, 1363–1366 (1995)

    Article  CAS  ADS  Google Scholar 

  11. Abzhanov, A. & Kaufman, T. C. Crustacean (malacostracan) Hox genes and the evolution of the arthropod trunk. Development 127, 2239–2249 (2000)

    CAS  PubMed  Google Scholar 

  12. Li, X. & McGinnis, W. Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution. Proc. Natl Acad. Sci. USA 96, 6802–6807 (1999)

    Article  CAS  ADS  Google Scholar 

  13. Gonzalez-Reyes, A. & Morata, G. The developmental effect of overexpressing a Ubx product in Drosophila embryos is dependent on its interactions with other homeotic products. Cell 61, 515–522 (1990)

    Article  CAS  Google Scholar 

  14. Mann, R. S. & Hogness, D. S. Functional dissection of Ultrabithorax protein in D. melanogaster. Cell 60, 597–610 (1990)

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  16. Vachon, G. et al. Homeotic genes of the bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Cell 71, 437–450 (1992)

    Article  CAS  Google Scholar 

  17. Chan, S. & Mann, R. S. The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences. Genes Dev. 7, 796–811 (1993)

    Article  CAS  Google Scholar 

  18. Galant, R. & Carroll, S. B. Evolution of a transcriptional repression domain in an insect Hox protein. Nature advance online publication, 6 February 2002 (DOI 10.1038/nature717).

  19. Fiol, C. J., Mahrenholz, A. M., Wang, Y., Boeske, R. W. & Roach, P. J. Formation of protein kinase recognition sites by covalent modification of the substrate. J. Biol. Chem. 262, 14042–14048 (1987)

    CAS  PubMed  Google Scholar 

  20. Jaffe, L., Ryoo, H. & Mann, R. S. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Genes Dev. 11, 1327–1340 (1997)

    Article  CAS  Google Scholar 

  21. Fienberg, A. A. et al. Phylogenetically conserved CK-II phosphorylation site of the murine homeodomain protein Hoxb-6. J. Exp. Zool. 285, 76–84 (1999)

    Article  CAS  Google Scholar 

  22. Li, C. & Manley, J. L. Allosteric regulation of Even-skipped repression activity by phosphorylation. Mol. Cell 3, 77–86 (2000)

    Article  Google Scholar 

  23. Grenier, J. K., Garber, T. L., Warren, R., Whitington, P. M. & Carroll, S. Evolution of the entire arthropod Hox gene set predated the origin and radiation of the onychophoran/arthropod clade. Curr. Biol. 7, 547–553 (1997)

    Article  CAS  Google Scholar 

  24. Kelsh, R. R. O. J. W., White, R. A. H. & Akam, M. Homeotic gene expression in the locust Schistocerca: An antibody that detects conserved epitopes in ultrabithorax and abdominal-A proteins. Dev. Genet. 15, 19–31 (1994)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank P. Hau, S. Romanowsky, D. DeRoma and E. Tour for help with the experiments, advice, and comments on the manuscript. The Bloomington Stock Center efficiently provided numerous fly stocks. We thank J. Moore for providing a culture of Folsomia candida and R. Burton for providing a culture of Tigriopus californicus. We also thank R. Galant and S. Carroll for communicating results before publication. This work was supported by a research grant from the National Institute of Child Health/Human Development to W.M.

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Correspondence to William McGinnis.

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Ronshaugen, M., McGinnis, N. & McGinnis, W. Hox protein mutation and macroevolution of the insect body plan. Nature 415, 914–917 (2002). https://doi.org/10.1038/nature716

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