Myostatin, also known as “the Speed Gene” is a gene located on Chromosome 18 of the horse. The gene encoding myostatin was discovered in 1997 by geneticists Dr. Se-Jin Lee and Alexandra McPherron who also produced a strain of mutant mice that lacked the gene. These myostatin “knockout” mice had approximately twice as much muscle as normal mice and were subsequently named “mighty mice”.
Myostatin is an interesting gene in that it is a regulator of expression. It is a gene whose role is to suppress muscle growth, so changes it in have a direct influence on muscularity and muscle fiber type. In Whippets, as you can see from the photos below, like the “mighty mice” those that have a deletion of myostatin (the mh/mh examples) grow muscle at significantly different rates to those that have no deletion (+/+). The double muscled whippets, also known as “bully whippets” have a deletion of some of the genetic code within Myostatin which means that their muscle development is unregulated. The bully whippets are useless for racing. However those whippets with a single copy of the deletion (mh/+) are significantly better runners than those that do not have a copy of the deletion.
Thankfully no such deletion is present in thoroughbreds. However, there are some changes in genetic code in and around the myostatin gene that have an effect on best race distance in the thoroughbred.
In 2010 Hill, et al identified a change in genetic code (a SNP), located at 66,493,737 on Chromosome 18 within myostatin (MSTN) itself that was associated with best racing distance in the Thoroughbred. Around the same time using a genome wide association test, Binns, et al found a SNP just outside the MSTN gene that had a relationship to best racing distance in North American thoroughbreds. Shortly after that using microsatellites Tozaki, et al found two SNPs located downstream of the MSTN gene to be associated with best race distance in the Japanese thoroughbred. A subsequent paper in 2011 by Tozaki et al brought further clarity to the variations within genes associated with best racing distance in Thoroughbreds and a greater understanding on how difficult assigning best race distance is.
Tozaki found that four SNPs that were associated with racing performance were located near the MSTN gene. Similar to Hill, they found that the SNP located at 66,493,737 in myostatin had no relationship to racetrack performance, just best race distance (hence why the term speed gene is a little misleading, but “distance gene” doesn’t have the same ring to it). However, they found that their two downstream SNPs not only had a relationship to best race distance but also elite performance. Their summation was that the use of multiple SNPs may lead to a more accurate genetic prediction of best race distance.
The combination of variants as an optimal description of best race distance is also what we have found in our studies. Using one variant to describe best race distance isn’t accurate and can lead to miss-classification of horses. As an example the SNP located at 66,493,737 has heterozygotes (C:T) of the following:
- Soldier’s Tale, a winner of the July Cup over 6f/1200m is a C:T on that SNP.
- Sebring, a winner of the Golden Slipper Stakes over 6f/1200m is a C:T on that SNP
- New Approach, a winner of the English Derby over 12f (2400m) is a C:T on that SNP
Using this one SNP, the hetrozygous version of this (C:T) gives us three totally different horses in terms of best race distance. This tells us that this particular SNP alone doesn’t do the best possible job in describing the best race distance of a racehorse.
A more recent study by Petersen, et al found that gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant (SINE insertion) and the intronic SNP (at 66,493,737) of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection of the area including and surrounding myostatin. In a further paper Petersen suggested that the SINE insertion, rather than the intron 1 SNP, is driving the observed muscle fiber type characteristics and is the variant targeted by selection for short-distance racing.