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

Abstract

Hox genes are central to the specification of structures along the anterior-posterior body axis 1,2 , and modifications in their expression have paralleled the emergence of diversity in vertebrate body plans 3,4 . 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 loci 5 , 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.In many animal species, Hox genes are clustered, and their expression domains, in both time and space, reflect their respective genomic order 1 . Although this genetic system has been used as a paradigm in the study of the evolution of body plans 6 , recent studies have highlighted an unexpected diversity in Hox gene number, genomic organization and expression patterns 7,8 . In tetrapods, these genes are classified into 13 groups of paralogy and are tightly clustered at four loci: HoxA to HoxD. A clear correspondence between particular Hox groups and defined morphological boundaries along the anteroposterior axis has been documented, either by comparing expression profiles between various vertebrates or by genetic experiments in the mouse 1,3,4,9 .Vertebrate species have highly variable number of vertebrae, ranging from fewer than ten to several hundreds 10-12 , a parameter that is probably dependent on the speed of the segmentation clock relative to axial growth, as proposed for snakes 13 . Within reptiles, squamates (that is, lizards and snakes) have a large realm of morphologies, suggesting that Hox genes were modified, either in their structure or in their regulation. Previous expression analyses in snakes showed an expansion of anterior Hox gene expression along the body axis, in parallel with body plan elongation 9 , and revealed that collinearity was fully respected 14 . However, these studies involved selected genes, in the absence of genomic information. Here we describe how structural and regulatory adaptations in this gene family may have accompanied the transition towards such a body plan and suggest that the unexpected invasion of all Squamata Hox clusters by transposons might have facilitated such adaptations.We characterized the genomic organization of posterior Hox loci in the corn snake (Pantherophis guttatus) and other reptiles, including the turtle, tuatara and several lizards, with a particular focus on repeated elements that are generally excluded from these loci in tetrapods but are abundan...

Tetrapod-like axial regionalization in an early ray-finned fish

“…In tetrapods, this region involves the first vertebra articulating with the pelvis and several subsequent elements morphologically and/or positionally distinct from the caudal series, sometimes referred to as postsacral or urostylic in amphibians (and early tetrapods) (figure 2) [3,6,14,17].…”

The chromatin insulator CTCF and the emergence of metazoan diversity

“…This site (Fig. 3B, site 2) lies within a highly conserved 57-bp stretch and has been implicated in morphological alterations during squamate evolution (59,60), suggesting that phenotypic variation can be a consequence of altered CTCF binding. Similarly, it has been proposed for humans that phenotypic variation can be caused by differences in transcription factor binding, including CTCF (61).…”

“…Although this has been shown at one site in D. melanogaster (42), a definite proof is missing in vertebrates. Work on the RXII regulatory element (59,60) suggests that it might also be true in these organisms. Similarly, impairment of CTCF itself should induce Hox gene misexpression.…”

The transposable element profile of the Anolis genome

“…This raises the intriguing possibility that transposons have played a significant role in the diversification of a morphologically diverse genus such as Anolis, and possibly could explain the large diversity of form and shape in reptiles. 38 …”