Speed and stamina: a tale of two genes

A project bringing together researchers from six different institutions indicates that a particular variation of the gene group called myostatin, which is partly responsible for the impressive speed of the world’s highest-performing thoroughbred racehorses, has been present in the lineage of some thoroughbred horses for at least three centuries and may have come from one particular mare

The findings, published today in the online journal Nature Communications, emerged from a study of the DNA of hundreds of living horses – including thoroughbreds and many of the world’s native breeds – as well as ancient DNA extracted from the skeletons of elite historic horses, among them the legendary Eclipse, one of the most famous horses of all time.

The research was led by Dr Emmeline Hill, a genomics scientist at University College Dublin (UCD) and Dr Mim Bower, an archaeo-geneticist at the University of Cambridge. The other institutions contributing to the study were Equinome Ltd, the Swedish University of Agricultural Sciences, the Smurfit Institute of Genetics, and the Russian Academy of Sciences.

The study shines new light on the interplay between speed and stamina in thoroughbreds, and how the two have been manipulated by humans through many generations of selective breeding. It will intrigue horse-lovers round the world as the single mare thought to have been responsible for introducing the speed gene may have been a British native horse. Many native breeds are now extinct but they shared their genetic make-up with some of the hardy pony types that have survived until today, such as the Dartmoor and Shetland.

Dr Bower’s work at Cambridge's McDonald Institute for Archaeological Research focuses on the relationship between humans and other animals – and how they have shaped each other. In the wild, horses need both speed and stamina to outrun their predators. Horses were domesticated around 7,000 years ago – and racing may have followed soon after. In the fiercely-competitive environment of the racetrack, success is determined by a combination of both speed and stamina in proportions varying according to the distances raced.

At the turn of the 18^th century a group of wealthy English landowners famously imported three stallions from the Middle East – the Darley Arabian, Godolphin Arabian and Byerley Turk – which were crossed with a total of 74 predominantly British and some imported mares. All thoroughbreds are descended from these foundation horses – and ever since details of their lineages have been carefully recorded, most notably in the General Stud Book, thus creating an extraordinarily valuable resource for today’s researchers.

For more than 300 years, breeders and trainers have striven to produce horses with the perfect combination of speed and stamina. Performance on the track is a matter of environment, management and training as well as breeding. However, it has long been accepted that there are underlying genetic factors that influence a horse’s capabilities as an athlete. Breeders have always used their intimate knowledge of winning lines to produce successful horses. Sophisticated DNA analysis techniques now allow scientists to look at the genetic make-up of both living and historic horses.

In 2010 Dr Hill and colleagues at UCD showed that a variant of myostatin – a gene group that usually inhibits muscle differentiation and growth – was partly responsible for elite race performance in thoroughbred horses. These findings led Dr Hill to team up with Dr Bower and others to launch a follow-up study exploring the origins of this genetic component in the ancestry of the modern thoroughbred, going right back to the foundation stages of the breed in the late 17^th century.

The researchers traced the gene variant backwards in time by screening the myostatin genes of hundreds of living horses, including some of the current stars of the racing world, and the skeletons of 12 historic thoroughbred horses held in archives round the country. Their results strongly suggest that the speed variant of myostatin entered the thoroughbred gene pool only once, around 300 years ago, and is likely to have come from a British native mare – perhaps one of the strong and stocky breeds of mountain and moorland ponies that thrived in the tough setting of Northern England and Scotland.

Speed and stamina are associated with two different variations of the myostatin gene complex: the C:T variant (known as C-gene) for speed and the T:T variant (known as T-gene) for stamina. In the early days of horse racing, contestants raced head-to-head over long distances – up to four miles – with the winner determined by a series of two-horse heats. Outstanding stamina was vital to a winner. Many elite horses – including Eclipse - have been shown to have two copies of the T-gene.  Breeders progressively selected for stamina over distance and thus, unwittingly, maintained high levels of the T-gene in the thoroughbred population.

From the mid-19^th century onwards, races became shorter with a greater number of runners and, at the same time, the racing industry began staging races for very young horses, with thoroughbreds increasingly starting their careers as two-year-olds.  The combination of young horses running over short distances favours animals which mature early in terms of musculature and develop the capacity to sprint in intensive high-speed bursts.

As the ideal speed/stamina balance shifted, breeders began selecting for sprinting ability, thus favouring the rarer C-gene over the more commonly found T-gene. The researchers have been able to pin the recent spread of the C-gene to Nearctic, a horse foaled (born) in Canada in the mid-1950s. Nearctic’s phenomenal record on the racetrack made him a sought-after stallion. Among others, he sired (fathered) Northern Dancer, another legendary winner, who once retired went on to sire (father) many other high-performing horses, thus rapidly disseminating the C-gene among elite horses all over the world.

Once the researchers knew they were looking for the origin of the C-gene rather than the T-gene that appears in all of the historic elite stallions they studied, they knew without a doubt that they needed to look at the female line.

As Dr Bower explains: “Our findings point to a British mare – one of the mares crossed with the three foundation stallions or their early descendants – being the most likely source of the original C-gene for speed because one of the lines of evidence from the research demonstrates that the prize-winning foundation stallions of the 17^th and 18^th centuries had two copies of the T-type speed gene which is linked to stamina rather than one copy of the C-type and one copy of the T-type associated with speed.”

To identify more precisely where the C-type gene variant originated, the researchers analysed DNA samples from more than 20 horse breeds, that included representatives of local British and Irish horses, from which female Thoroughbred lineages derive, as well as exotic eastern populations from which male Thoroughbred lineages derive. They also looked at DNA from close relatives to horses, for example donkeys and zebras, to find out whether the C-gene existed in these equid species or was unique to horses. Zebras were of particular interest since they indicated which variant of the speed gene was present in wild equids, something that is impossible to study in horses since the wild ancestors of our domestic horses, including thoroughbreds, are long extinct.

“What’s fascinating is that the study revealed that the Shetland breed – the sturdy little pony immortalised by the Thelwell cartoons – has the highest frequency of the C-type gene variant among the horses whose DNA we screened.  The Shetland represents just one of many local British horse types, which, according to historical sources, were highly prized for their racing ability before the Thoroughbred line was formally established. We’re not suggesting that Shetlands were speedy in themselves but rather that their genes have made a key contribution to the thoroughbred line,” said Dr Bower.

“By comparing the diversity of chromosomes around the C and T type variants of the myostatin gene in horses, we found only a single C-type compared with 11 different T-type gene variants, meaning that the speed gene entered the Thoroughbred line just once. This is remarkable because it illustrates the genetic consequences of selection in action. Thanks to the science of genomics we can see the C-gene enter the Thoroughbred gene pool, and then, with the help of historic pedigree records and ancient DNA, we can watch its spread through the thoroughbred gene pool in 300 years of breeding.”

Since prehistory humans and other animals have been shaping each other and the environment. Dr Bower added: “The most recent project shows how quickly human selection can affect a population of animals. In less than 300 years, a new and extremely rare version of an essential gene becomes frequent in a group of horses that are closely managed by human social and cultural choices. We will never know the precise identity of the mare which introduced the C-type variant but the project has shown us that the British native breeds which formed the backbone of the thoroughbred line, and which have been so under-valued historically, were, in important ways, responsible for the outstanding racing ability that has made the thoroughbred so famous.”

The research was supported by grants from The Horserace Betting Levy Board, Leverhulme Trust, Cambridge Overseas Trust and Science Foundation Ireland.