The transition from water to land is one of the most fascinating enigmas of evolution. In particular, the evolution of limbs from ancestral fish fins remains a mystery.
This shows the expression of fish Hox genes in a mouse embryo.
Credit: Denis Duboule, UNIGE
Both fish and land animals possess clusters of Hoxa and Hoxd genes, which are necessary for both fin and limb formation during embryonic development. Denis Duboule's team, at the UNIGE and the EPFL, Switzerland, compared the structure and behavior of these gene clusters in embryos from mice and zebrafish.
The researchers discovered similar 3-dimensional DNA organization of the fish and mouse clusters, which indicates that the main mechanism used to pattern tetrapod limbs was already present in fish. However, when inserted into transgenic mouse embryos, the fish Hox genes were only active in the mouse arm but not in the digits, showing that the fish DNA lacks essential genetic elements for digit formation.
The study, published in the January 21, 2014 edition of PLoS Biology, thus concludes that, although the digital part of the limbs evolved as a novelty in land animals, this happened by elaborating on an ancestral, pre-existing DNA infrastructure.
Our first four-legged land ancestor came out of the sea some 350 million years ago. Watching a lungfish, our closest living fish relative, crawl on its four pointed fins gives us an idea of what the first evolutionary steps on land probably looked like. However, the transitional path between fin structural elements in fish and limbs in tetrapods remains elusive.
An ancestral regulatory strategy …
In animals, the Hox genes, often referred to as 'architect genes', are responsible for organizing the body structures during embryonic development. Both fish and mammals possess clusters of Hoxa and Hoxd genes, which are necessary for fin and limb formation. The team of Denis Duboule, professor at the University of Geneva (UNIGE) and the Ecole polytechnique fédérale de Lausanne (EPFL), Switzerland, had recently shown that, during mammalian development, Hoxd genes depend on a 'bimodal' 3-dimensional DNA structure to direct the development of the characteristic subdivision of the limbs into arm and paw, a division which is absent from fish fins.
'To determine where the genetics behind this subdivision into 'hand' and 'arm' came from during evolution, we decided to closely compare the genetic processes at work in both fin and limb development', says Joost Woltering, researcher at the Department of Genetics and
Evolution of the UNIGE Faculty of Science and lead author of the study. Surprisingly, the researchers found a similar bimodal 3-dimensional chromatin architecture in the Hoxd gene region in zebrafish embryos. These findings indicate that the regulatory mechanism used to pattern tetrapod limbs probably predates the divergence between fish and tetrapods. "In fact this finding was a great surprise as we expected that this 'bimodal' DNA conformation was exactly what would make all the difference in the genetics for making limbs or making fins" adds Joost Woltering.
…that just needs to be modernized
Does this imply that digits are homologous to distal fin structures in fish? To answer this question, the geneticists inserted into mice embryos the genomic regions that regulate Hox gene expression in fish fins. 'As another surprise, regulatory regions from fish triggered
Hox gene expression predominantly in the arm and not in the digits. Altogether, this suggests that our digits evolved during the fin to limb transition by modernizing an already existing regulatory mechanism', explains Denis Duboule.
'A good metaphor for what has probably happened would be the process of 'retrofitting', as is done in engineering to equip outdated machine frames with new technology. Only, in this case, it was a primitive DNA architecture which evolved new 'technology' to make the fingers and toes', says Joost Woltering.
Fin radials are not homologous to tetrapod digits
The researchers conclude that, although fish possess the Hox regulatory toolkit to produce digits, this potential is not utilized as it is in tetrapods. Therefore, they propose that fin radials, the bony elements of fins, are not homologous to tetrapod digits, although they rely in part on a shared regulatory strategy.
New lines of investigation are to find out exactly what has changed between the DNA elements in fish and tetrapods. 'By now we know a lot of genetic switches in mice that drive Hox expression in the digits. It is key to find out exactly how these processes work nowadays to understand what made digits appear and favor the colonization of the terrestrial environment', concludes Denis Duboule.
Denis Duboule | EurekAlert!
New supercomputer simulations enhance understanding of protein motion and function
24.11.2015 | DOE/Oak Ridge National Laboratory
Sensor sees nerve action as it happens
24.11.2015 | Duke University
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...
AWI researchers’ unique 15-year observation series reveals how sensitive marine ecosystems in polar regions are to change
The warming of arctic waters in the wake of climate change is likely to produce radical changes in the marine habitats of the High North. This is indicated by...
Berkeley Lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier
Glioblastoma multiforme, a cancer of the brain also known as "octopus tumors" because of the manner in which the cancer cells extend their tendrils into...
17.11.2015 | Event News
21.10.2015 | Event News
20.10.2015 | Event News
24.11.2015 | Trade Fair News
24.11.2015 | Trade Fair News
24.11.2015 | Life Sciences