Not Exactly Rocket Science

Genes that code for proteins, like FGF4, first need to be transcribed into a molecule called messenger RNA (mRNA). A group of enzymes called ribosomes "read" this transcript and assemble a chain of amino acids - a protein - based on the information it encodes. That's the usual story, but sometimes, an mRNA molecule is converted back into DNA through a process called reverse transcription; some viruses have the ability to do this.

The DNA molecule can then be inserted back into the genome it was originally transcribed from, often in a new place. But to be active, these reinserted genes need to be surrounded by the right "promoter" sequences. Without these promoters, most inserted genes just sit around doing nothing, slowly building up debilitating mutations. However, a lucky few hop back into just the right place where they can "borrow" promoters from other parts of the genome. They can go on to produce functional proteins and these active copies are called retrogenes.

Parker found clear evidence that the extra FGF4 of dachshunds and corgis is indeed a retrogene. When genes are transcribed into mRNA, useless chunks of sequence called introns are edited out of the transcript. An mRNA molecule that is then reverse-transcribed would produce a shorter, more streamlined stretch of DNA than its original gene. That's exactly what the second FGF4 of short-legged dogs is - an intron-less version of the original.

Parker's team isn't yet clear what this extra copy of FGF4 does to stunt the growth of their bearers, but they have a very good idea. They suggest that with two copies of the gene, the dogs overproduce the FGF4 protein, which docks at, and turns on, another protein called FGFR3. In humans, overactive FGFR3 is responsible for virtually every case of achondroplasia, the most common type of dwarfism. It seems that FGFR3 and its partner proteins are responsible for shortness in both man and man's best friend.

The short-legged varieties were developed in many different countries and they don't sit on an exclusive branch of the dog family tree. Nonetheless, the sequence of the FGF4 retrogene strongly implies that it arose only once, very early on in the evolution of domestic dogs and before they split into the various modern breeds.

This means that for the longest time, domestic dogs had the potential for dwarfism, which was independently maintained and nurtured by breeders all over the world. Originally, they were shaped for specific jobs like flushing out burrowing animals. Later on, breeders would have kept imposing strong evolutionary pressure on their animals to meet the conditions set by dog-breeding associations. The big question is whether a single retrogene can be as potent as force in the evolution of wild species as it so clearly has been in a single domestic one.

Reference: Science 10.1126/science.1173275

Image: Dachshund by Lily M; image by Science/AAAS

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