Scientists find genetic gap between limbs, fins

LOS ANGELES – A change in just one gene may have jump-started the transition of ancient fish into animals that could move on land – by deleting a fin and replacing it with the rudiments of a limb, scientists reported today in the journal Nature.

Marie-Andree Akimenko and co-workers at the University of Ottawa identified a set of genes that was absent in tetrapods, the animals with four limbs that descended from fish, but present in all seven species of fish they investigated.

The scientists blocked the activity of these genes in a small stripy fish called a zebrafish, which is commonly used in lab research. The resulting fish had stunted fin growth. Effects were apparent as early as two days after fertilization, at which point the structure that normally goes on to form the skeletal foundation of the fin was completely missing. This suggested that inactivating the genes provides a blank canvas for an entirely new structure.

The genes also appear to play a role in digit development. The fossil record shows that the earliest tetrapods had eight digits, which over time slowly decreased to the maximum of five seen today. The genetic program of the modified zebrafish looked like it was heading toward having many digits, like the early tetropod ancestors.

The study is important, the scientists said, because it suggests how a pivotal step in the evolution of life may have occurred.

“I think it is really exciting that here we have this gene that obviously seems critical for fin development and it’s lost in tetrapods,” said Yale University biologist Scott Weatherbee, who studies limb development. “It really makes sense.”

There are a few complications that still need to be smoothed out. For one thing, to affect the fin, the researchers needed to inactivate two similar genes in the zebrafish, an event that would be unlikely to occur naturally. The team suspects that the ancient fish ancestor only had one copy of this gene and that the second copy appeared later through a duplication in the modern fish lineage.

Second, if the loss of this gene was the first step to limb development, the resulting fish probably would have had very short fins. Since such a fin would probably have put them at an evolutionary disadvantage, how they survived until further genetic modifications furnished more functional limbs remains an open question.