How the way horses move can tell us about the genetics of limb coordination

Most horses naturally use three gaits: the walk, the trot and the gallop. But some breeds have additional gaits. For example, some Icelandic horses can pace and tölt. In the pace, like in the trot, two feet are always off the ground but, unlike the trot where diagonal front and hind legs move forward and backward together, the two legs on the same side move together. In the tölt, only one foot is completely off the ground at any one time and the horse moves its left hind leg forward first, then its left fore leg, its right hind leg and finally its right front leg. The ability of Icelandic horses to pace is highly heritable, which means it is strongly determined by genetic factors. Researchers set out to discover these factors and identified a mutation that allow horses to use other gaits than the three classical ones, in a gene critical for the development in mice of networks of neurons that control limb coordination.

A pacing horse Image credit: Eadweard Muybridge via Wikimedia Commons

The DNA of two individuals of the same species are not identical. For instance about 3 million nucleotides are different between two human beings. These differences partly determine the physical and physiological characteristics of an individual so the addition of all these differences contributes to what makes each one of us unique. But when looking at one specific characteristic and the nucleotide that influences it, the individuals that have the same nucleotide should share the same characteristic. A method called genome wide association study uses this fact to unravel the genetic differences behind individual’s characteristics. It takes two groups of individuals, one group that has the characteristic while the other does not, and compare the nucleotide differences of the two groups. If one of the differences is more frequent in the group with the characteristic, this difference is associated with the characteristic, which means either this difference or another one close-by is responsible for the characteristic.

Using this method, one group of Icelandic horses that could tölt and pace and another group that could only tölt, scientists identified a nucleotide difference associated with the ability to pace. This difference marked a 684-nucleotide region of the horse genome as the place where to look for the genetic factor behind pacing.
Sequencing of this region in the two different type of horses revealed 65 differences unique to the pacing horses, one of which caused a shorter DMRT3 protein to be expressed. Looking at about 350 other Icelandic horses they found that all pacing horses were homozygous for this difference, that is both copies of their DMRT3 gene had the mutation that truncates the protein, while that was the case for only about 30% of the horses that could not pace.

Other horse breeds such as the Paso Fino and Rocky Mountain horses also use different types of gait. In these breeds as well, the DMRT3 mutation was more frequent while it was absent in breeds that only have the three classical gaits. It could be because this mutation is disadvantageous for other gaits. Mutant Icelandic horses do not perform as well as non-mutants in trot and gallop. The DMRT3 mutation might have been selected against in breeds specifically developed for activities where trot and gallop are used such as dressage, show jumping and gallop races. However, it might give horses an advantage for harness racing. American Standardbred horses, especially bred for harness racing, are all homozygous for the mutation and Swedish Standardbred mutant horses win more races and are considered better breeders for racing performance. So not only does the DMRT3 mutation in horse facilitates the use of additional gaits but it may also promote the ability to pace or trot at high speed as in harness racing.

The scientists then turned to mice lacking the DMRT3 gene to investigate its role in the networks of neurons that control locomotion. The spinal cord of mammals contains neuronal networks called central pattern generators because they control the signals that result in the left-right alternation of limbs and the activation of the muscles that coordinate limb movements. While these signals have a stable rythm and are coordinated in normal mice, the ones in mice with a deleted DMRT3 gene lack regularity and coordination. Neurons in the spinal cord are classified in different populations depending on the genes they express. DMRT3 is expressed in one specific population and when it is not expressed as in mice lacking the DMRT3 gene, the gene expression of this population changes, which could modify the development of these neurons.

And that’s how you get from the different ways horses can move to the discovery of a gene important for the normal development of the neuronal networks that coordinate limb movements.

Andersson et al. (2012). Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature, 488, 642-646 DOI: 10.1038/nature11399


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