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Hox protein mutation and macroevolution of the insect body plan


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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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).

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