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Evolution of the snake body form reveals homoplasy in amniote Hox gene function

Nature volume 520, pages 86–89 (2015)Cite this article

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Abstract

Hox genes regulate regionalization of the axial skeleton in vertebrates1,2,3,4,5,6,7, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms8,9,10,11,12,13,14. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox gene expression domains9, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions10,11,12,13. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phylogenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior–posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number15, not by changes in the function of primaxial Hox genes9,10.

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Figure 1: Morphological variation in the pre-cloacal vertebral column of limbed lizards and snakes.
Figure 2: Regional boundaries, evolutionary models of regional changes, and intracolumnar variance.
Figure 3: Correspondence between Hox expression domains and morphometric boundaries for four-region models of primaxial regionalization.
Figure 4: Time-calibrated phylogeny of selected extant and fossil amniotes, illustrating pre-cloacal and pre-sacral primaxial skeletal regionalization and the generalized ancestral amniote pattern of Hox expression.

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Acknowledgements

We thank K. DeQueiroz, G. Zug, R. McDiarmid, K. Seymour, D. Gower, C. McCarthy, C. Bell, H. Voris, C. J. Cole, P. Holroyd and T. Labedz for specimen access, A. K. Behrensmeyer for access to microscopy facilities, and A. Goswami, K. Johnson, P. Mitteroecker, R. Raff, R. Reisz and M. Rowe for useful comments and discussion. This work was supported in part by a US National Science Foundation Postdoctoral Fellowship in Biological Informatics (DBI-0204082) to J.J.H., a Natural Sciences and Engineering Research Council of Canada Discovery Grant to J.J.H., and a US National Science Foundation Grant (EAR-0843935) to P.D.P.

Author information

Authors and Affiliations

  1. Department of Earth and Atmospheric Sciences and Nebraska State Museum of Natural History, University of Nebraska–Lincoln, Lincoln, 68588-0340, Nebraska, USA

    Jason J. Head

  2. Departments of Geological Sciences, Biology and Anthropology, Indiana University, Bloomington, 47405-1405, Indiana, USA

    P. David Polly

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  1. Jason J. Head
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Contributions

J.J.H. and P.D.P. designed the study. J.J.H. and P.D.P. collected morphometric data. J.J.H. and P.D.P. conducted morphometric analysis. P.D.P. designed and conducted segmented linear regression and maximum-likelihood analyses. J.J.H. and P.D.P. prepared figures and wrote the manuscript.

Corresponding authors

Correspondence to Jason J. Head or P. David Polly.

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Competing interests

The authors declare no competing financial interests.

Additional information

Morphometric data have been deposited in Dryad (http://dx.doi.org/10.5061/dryad.jq285).

Extended data figures and tables

Extended Data Figure 1 Skeletal morphology and intracolumnar shape variation in the pre-cloacal vertebral column of limbed lizards and snakes.

a, Skeleton of limbed lizard (Pogona minor) in dorsal view. b, Skeleton of snake (Hypsiglena torquata) in dorsal view. c, Principal component analysis (PCA) ordination of pre-cloacal vertebral shape variables derived from geometric morphometric analysis in a limbed lizard (Pogona vitticeps) based on first two principal components (PC 1 and PC 2). d, PCA ordination of pre-cloacal vertebral shape variables in a snakes (Pantherophis guttatus). Ordination using the first two components describes intracolumnar shape change along the anterior–posterior axis of the pre-cloacal vertebral column and explains >90% of overall shape variation.

Extended Data Figure 2 Model fitting with segmented linear regression.

a–f, A series of regional models were fit to each taxon using a series of segmented linear regressions. In each case vertebral shape variables (orange dots) were regressed onto position in the vertebral column (brown lines). Models differ in both the number of regions and the position of regional boundaries. a–f, Two examples are shown for each of two, three and four regions, where the right column shows the best fitting example for each. Red arrows mark the regional boundaries in each example. The slope of each segment (heavy dark line) represents the shape gradient each region and the residual sum of squares (RSS) represents the lack of fit of the model to the data. f, The model with the highest likelihood. The log likelihood of each model is proportional to this model. However, the number of parameters increases with the number of regions, as does the likelihood of the model; therefore corrected Akaike adjustment (AICc) is required to select the best model. b, The best model using AICc. It is the two-region model with the breakpoint 25% along the pre-cloacal vertebral column. This example is based on the first principal component of Eunectes notaeus.

Extended Data Figure 3 Morphometric landmarks used to quantify primaxial shape variance and regionalization in pre-cloacal vertebrae of Mus and Alligator.

a, b, Elements for both Mus (a) and Alligator (b) are, from top to bottom: first post-atlanto-axial vertebrae, third thoracic (Mus) and sixth dorsal vertebrae (Alligator), last lumbar vertebrae. See Extended Data Table 2 and Supplementary Information for description of landmarks and discussion of landmark selection.

Extended Data Figure 4 Best-fit regionalization models for complete pre-cloacal skeletons of Mus, Alligator and select squamates.

AICc scores are reported for the best regional model from each taxon. Taxa in bold are snakes or have snake-like body forms. Cells represent individual vertebrae in each region for the complete pre-cloacal/pre-sacral vertebral column in each taxon. Cell colours represent morphometric regions. C, cervical; L, lumbar; T, thoracic.

Extended Data Figure 5 Comparison of best-fit four-region model with models fitting morphometric regional boundaries to expression boundaries for Hox10 genes.

a, Best-fit model. b, Fit to anterior expression boundaries of HoxA10 and HoxC10 from ref. 12. c, Fit to anterior expression boundary for HoxC10 from ref. 10. d, Fit to posterior expression boundaries of HoxA10 and HoxC10 from ref. 12. Abbreviations are the same as for Fig. 3. Only the posterior boundaries of Hox10 expression are significantly worse fits than the best-fit model. RSS, residual sum of squares for segmented linear regression. P values are probability that the Hox boundaries differ from the best regional model.

Extended Data Table 1 Examined specimens
Full size table
Extended Data Table 2 Landmarks and corresponding morphology used in morphometric analysis
Full size table
Extended Data Table 3 AICc values for regionalization models
Full size table
Extended Data Table 4 AICc values for regionalization models
Full size table

Supplementary information

Supplementary Information

This file contains Supplementary Discussions 1-2, the data acquisition details for the methods, the data sources for the figures and additional references. (PDF 172 kb)

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Head, J., Polly, P. Evolution of the snake body form reveals homoplasy in amniote Hox gene function. Nature 520, 86–89 (2015). https://doi.org/10.1038/nature14042

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