The evolution of limbs has been a long-standing scientific mystery; new research suggests the appendages developed when a DNA structure present in both humans and land animals was modernized.
Both aquatic and land dwelling animals posses "Hoxa and Hoxd genes." These genes are essential in the formation of both fins and limbs in the embryonic stage, a Université de Genève news release reported.
Researchers compared the behavior of these genes in both mice and zebrafish, and found the same DNA clusters that were necessary for limb formation were present in the fish as well. They found the main "mechanism" worked to pattern tetrapod limbs existed in the zebrafish; when the fish Hox genes were inserted into a mouse embryo it proved to have the ability to form limbs but not digits. This means 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," the news release reported.
Aquatic creatures are believed to have started walking on land about 350 million years ago. Our closest "living fish relative" is the lungfish, which can walk on land on the tips of its fins in what is believed to be a replica of those first ancient steps.
The Hox genes (nicknamed "'architect genes") organize bodily structures during embryo development.
A study by Denis Duboule, professor at the University of Geneva (UNIGE) and the Ecole polytechnique fédérale de Lausanne (EPFL) recently showed the during mammals' embryonic stage the Hoxd genes rely on a "bimodal" 3-dimensional DNA structure to create the subdivision between arm and paw; this division does not exist in fish.
"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', Joost Woltering, researcher at the Department of Genetics and Evolution of the UNIGE Faculty of Science and lead author of the study, said in the news release.
The team found a similar "bimodal 3-dimensional chromatin architecture" in the zebrafish's Hoxd gene regions. They concluded that the "mechanism used to pattern tetrapod limbs probably predates the divergence between fish and tetrapods," the news release reported.
"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," Woltering said.
"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," Woltering said.
The team concluded that fish do not utilize the "Hox regulatory toolkit" to form digits. Fin radials (bones in the fin) are not believed to homologous to tetrapod digits.
In the future researchers hope to uncover more differences between fish and tetrapod DNA.
"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," Duboule said.
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