Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland. School of Life Sciences, Federal Institute of Technology, Lausanne, Switzerland. School of Life Sciences, Federal In...
The evolution of tetrapod limbs from fish fins enabled the conquest of land by vertebrates and thus represents a key step in evolution. Despite the use of comparative gene expression analyses, critical aspects of this transformation remain controversial, in particular the origin of digits. Hoxa and Hoxd genes are essential for the specification of the different limb segments and their functional abrogation leads to large truncations of the appendages. Here we show that the selective transcription of mouse Hoxa genes in proximal and distal limbs is related to a bimodal higher order chromatin structure, similar to that reported for Hoxd genes, thus revealing a generic regulatory strategy implemented by both gene clusters during limb development. We found the same bimodal chromatin architecture in fish embryos, indicating that the regulatory mechanism used to pattern tetrapod limbs may predate the divergence between fish and tetrapods. However, when assessed in mice, both fish regulatory landscapes triggered transcription in proximal rather than distal limb territories, supporting an evolutionary scenario whereby digits arose as tetrapod novelties through genetic retrofitting of preexisting regulatory landscapes. We discuss the possibility to consider regulatory circuitries, rather than expression patterns, as essential parameters to define evolutionary synapomorphies.
Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal.
Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins.
University of Geneva, Department of Genetics and Evolution, 30 quai Ernest Ansermet, 1211 CH, Geneve, Switzerland.
The elongated, snake-like skeleton, as it has convergently evolved in numerous reptilian and amphibian lineages, is from a developmental biologist's point of view amongst the most fascinating anatomical peculiarities in the animal kingdom. This type of body plan is characterized by a greatly increased number of vertebrae, a reduction of skeletal regionalization along the primary body axis and loss of the limbs. Recent studies conducted on both mouse and snakes now hint at how changes inside the gene regulatory circuitries of the Hox genes and the somitogenesis clock likely underlie these striking departures from standard tetrapod morphology, suggesting scenarios by which snakes and other elongated species may have evolved from more ordinarily bodied ancestors.
National Research Centre Frontiers in Genetics, Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland.
In the emerging discipline of Evo-Devo, the analysis of gene expression patterns can be deceptive without a clear understanding of the underlying regulatory strategies. Here, we use the paradigm of hand and foot evolution to argue that the consideration of the regulatory mechanisms controlling developmental gene expression is essential to resolve comparative conundrums. In this context, we discuss the adaptive relevance of evolving stepwise, distinct developmental regulatory mechanisms to build an arm, i.e., a composite structure with functional coherence.
National Research Centre 'Frontiers in Genetics', Department of Zoology and Animal Biology, University of Geneva, Switzerland.
A recent study in BMC Evolutionary Biology shows that many of the open reading frames in mammalian Hox genes are more conserved than expected on the basis of their protein sequence. The presence of highly conserved DNA elements is thus not confined to the noncoding DNA in neighboring regions but clearly overlaps with coding sequences. These findings support an emerging view that gene regulatory and coding sequences are likely to be more intermingled than once believed.