But that wasn’t the only relevant genome change that the researchers found. They also identified a mutation in an enhancer that regulates the expression of some genes in the developmentally important hox group. Hox genes specify the general body plan in all bilaterally symmetrical animals. One subset of them, the hoxa gene cluster, is usually expressed only in the posterior (back) edges of the developing fins and in limbs, where it specifies the formation of digits.
In the little skate, the hoxa genes were active in both the posterior and the anterior parts of the fin. It was as if the growth zone along the back of the fin had been duplicated along the front, so that the animal made a new set of structures on the anterior of the fin that was symmetrical with structures on the posterior, Debiais-Thibaud said.
Nakamura showed that the skate’s mutated enhancer was causing this new hoxa expression pattern. He combined the skate’s enhancer with a gene for a fluorescent protein and then inserted that gene combination into zebra fish embryos. The fish’s pectoral fins grew abnormally, and fluorescence appeared along both their leading and trailing edges, which showed that the skate’s enhancer was driving hoxa expression in both parts of the fin. When Nakamura repeated the experiment with an enhancer from a shark, the fin growth was unaffected and the fluorescence was limited to the posterior.
“So now we are thinking that the genetic mutations occurred specifically in the skate enhancer, and that can drive unique hox gene expression in skate fins,” Nakamura said.
Shaped for New Ways of Life
In the picture of skate evolution that the researchers have reconstructed, at some point after the skate lineage diverged from sharks, they acquired a mutation in an enhancer that made their hoxa genes active in both the front and the back of their pectoral fins. And within the new tissues growing along the anterior of the fin, genome rearrangements caused the PCP pathway to be activated by enhancers in a different TAD, which had the further effect of making the fin extend forward and fuse with the animal’s head.
“By forming the winglike structure, [the skates] are able now to inhabit a whole different ecological niche, the bottom of the ocean,” Amemiya explained.
Stingrays, mantas and other rays are closely related to skates (they are all classified as “batoid” fishes), and their similarly pancaked shape is probably due to the same genome rearrangements. The rays, however, have also modified their winglike fins in ways that basically allow them to fly through the water. “The skates have these undulations of the fin and stay on the bottom, but manta rays can come to the surface and have a whole different way of locomotion,” Amemiya said.
Although evolutionary developmental biologists have previously speculated that these changes in the 3D architecture of a genome might be possible, this is probably one of the first papers to clearly link them to fairly big changes in body shape, Marlétaz said.
Lupiáñez also believes the findings have significance that reaches far beyond an understanding of skates. “This is a completely new way to think about evolution,” he said. Structural rearrangements “can cause a gene to be activated in a place where it should not be.” He added: “This can be a mechanism of disease, but it can also serve as a driver of evolution.”