Spotted gar reveals origins of mammalian wrist and finger development

Chuck Bednar for redOrbit.com – Your Universe Online
While the fossil record has found that wrists and fingers have an aquatic origin, previous attempts to link fingers and fins have proven unsuccessful. Now, though, a team led by University of Chicago researchers has discovered the reason why: scientists were studying the wrong fish.
Writing in Monday’s edition of Proceedings of the National Academy of Sciences (PNAS), organismal biology and anatomy professor Dr. Neil Shubin and his colleagues explained that the found the basic genetic machinery for mammalian limb development in a non-model fish known as the spotted gar.
Since comparisons of fin and limb morphology had proven unsuccessful, they looked at the spotted gar using developmental and molecular data. The fish, whose genome had recently been sequenced, revealed that the regulatory networks controlling wrist-and-digit-building genes were deeply conserved between fish and tetrapods.
“Fossils show that the wrist and digits clearly have an aquatic origin,” Dr. Shubin explained in a statement. “But fins and limbs have different purposes. They have evolved in different directions since they diverged. We wanted to explore, and better understand, their connections by adding genetic and molecular data to what we already know from the fossil record.”
The earliest attempts to verify the link based on comparing the shapes of fin and limb bones proved unsuccessful. The wrist is made up of a series of small nodular bones followed by thin, longer bones that make up the digits. On the other hand, the bones of living fish feature a set of longer bones that end in smaller, circular ones known as radials.
The HoxD and HoxA clusters genes, which are responsible for shaping the bones, also differ. Dr. Shubin and his co-authors first tested the ability of genetic “switches” controlling these genes in bony, ray-finned fish called teleosts to shape the limbs of developing transgenic mice. These fish control switches did not trigger any activity in the autopod, however.
Teleosts are a widely-studied group of fish that includes nearly all commercial varieties of fish. However, the researchers soon realized that they were not ideal for comparison studies of how ancient genes were regulated. When it came to looking for genetic switches involved in wrist and digit-building, they found “a lack of sequence conservation” in these species.
The problem was traced back to radical change in teleost fish genetics which occurred over 300 million years ago, when the fish-like creatures that became tetrapods split off from other types of bony fish. At this time, a common ancestor of the teleost lineage experienced a whole-genome duplication (WGD) – a phenomenon that has taken place several times in evolution.
This WGD doubled the genetic repertoire of teleost fish and provided them with the potential for tremendous diversification, the study authors explained. This may have helped telosts to adapt to several different types of environments, and during this process, the genetic switches controlling autopod-building genes would up changing their function somewhat.
As a result, those genes became harder to identify in comparison to mice and other types of animals, lead author and University of Chicago graduate student Andrew Gehrke explained. Not all bony fishes went through this process, however, and as it turns out, the spotted gar was one of those that had split off from teleost fishes before the genome duplication event occurred.
When the investigative team compared Hox gene switches from the spotted gar with tetrapods, they discovered “an unprecedented and previously undescribed level of deep conservation of the vertebrate autopod regulatory apparatus.” They said that this seems to indicate a high degree of similarity between “distal radials of bony fish and the autopod of tetrapods.”
They tested this notion by taking the gene switches related to fin development from the spotted gar and inserted them into developing mice. The resulting patterns of activity were described as “nearly indistinguishable” from those driven from the mouse genome, leading the authors to conclude that their results “provide regulatory support for an ancient origin of the ‘late’ phase of Hox expression that is responsible for building the auto pod.”
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