Very recently, efforts have been made to understand the apparent plasticity of the canine genome [59]. Fondon and Garner propose that expansions and contractions of tandem repeats within coding sequences are a major source of phenotypic variation in dogs. As such, this mechanism serves to generate dogs with novel morphologies faster than would be otherwise predicted. To test their hypothesis, they sequenced 37 repeat-containing regions from 17 genes that were known or predicted to have a role in craniofacial development in 92 breeds of dogs. They found that the repeats in the dog were changing faster in terms of length than comparable repeats in humans. They also analyzed three-dimensional models of dog skulls from 20 breeds and some mixed-breed dogs, and found that variation in the number of repeats in the coding regions of the ALX4 and RUNX2 genes were quantitatively associated with significant differences in limb and skull morphology. The authors argue that the incremental effects of repeat length mutations would be an efficient way to generate the rapid yet morphologically conservative changes that distinguish various breeds of dog. If correct, this hypothesis would be in striking contrast to a commonly held view that variation arises largely from modification of gene regulatory sequences, such as transcriptional control elements. Several avenues of experimentation are suggested by this work, including studies of additional genes and more phenotypic measures. However, the initial data provide a starting point for relating novel features of the canine genome to repeated observations regarding rapid creation of morphologically distinct breeds.
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