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Changes in Hox genes’ structure and function during the evolution of the squamate body plan


Hox genes are central to the specification of structures along the anterior–posterior body axis1,2, and modifications in their expression have paralleled the emergence of diversity in vertebrate body plans3,4. Here we describe the genomic organization of Hox clusters in different reptiles and show that squamates have accumulated unusually large numbers of transposable elements at these loci5, reflecting extensive genomic rearrangements of coding and non-coding regulatory regions. Comparative expression analyses between two species showing different axial skeletons, the corn snake and the whiptail lizard, revealed major alterations in Hox13 and Hox10 expression features during snake somitogenesis, in line with the expansion of both caudal and thoracic regions. Variations in both protein sequences and regulatory modalities of posterior Hox genes suggest how this genetic system has dealt with its intrinsic collinear constraint to accompany the substantial morphological radiation observed in this group.

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Figure 1: Genomic organization of the posterior HoxD cluster.
Figure 2: Expression patterns of Hox13 and Hox10 genes in snake and lizard embryos.
Figure 3: Comparison of vertebrate HOX10 protein sequences.
Figure 4: Evolutionary modifications of the posterior Hox system in the whiptail lizard and corn snake.

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Data deposits

Sequences of genes described in this paper are deposited in GenBank under accession numbers GU320304 to GU320335.


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We thank A. Schmitz for sharing squamate tissues; A. Debry and F. Chabaud for technical assistance; and members of the Duboule and Milinkovitch laboratories for discussions and reagents. This work was supported by funds from the University of Geneva and the Federal Institute of Technology in Lausanne, the Swiss National Research Fund, the National Research Center (NCCR) ‘Frontiers in Genetics’, the EU programme ‘Crescendo’ and the ERC grant (to D.D.).

Author Contributions N.D.P. and D.D. designed the experiments and analysed the data. N.D.P. performed the experiments except those involving the tuatara, which were conducted by H.M. J.I.M.B. performed the phylogenetic analyses. M.C.M. produced and prepared snake embryos and O.P. provided snake and lizard embryos. N.D.P. and D.D. wrote the paper, and all co-authors contributed in the form of discussion and critical comments.

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Correspondence to Denis Duboule.

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Di-Poï, N., Montoya-Burgos, J., Miller, H. et al. Changes in Hox genes’ structure and function during the evolution of the squamate body plan. Nature 464, 99–103 (2010).

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