The Triple Crown of Genetics: Tracing the Genetics Path to Racing Greatness

May 3, 2024

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On the eve of May 4th, as many Americans prepare their derby day attire and mix mint juleps to enjoy while watching the 150th Kentucky Derby, we at Complete Genomics want to take a moment to honor the true stars of the event: the horses. Amidst the excitement of the ‘Most Exciting Two Minutes in Sports,’ it’s worth pausing to marvel at the incredible speed and power of American thoroughbreds, and to reflect on the extensive history of genetic refinement this remarkable species has undergone.

History of Domestication

The horse holds a unique position in human history, serving as a vital source of transportation, labor, and even influence on motion pictures. Despite their depiction in ancient cave paintings dating back to 30,000 BC, modern domestic horses were introduced after this time period and are believed to have replaced all local populations by 2000 BC, marking a significant milestone in the evolution of human civilization. From then on, the domestication of horses profoundly influenced various aspects of human life, with some civilizations building their entire culture around them.

Over the centuries, horses transitioned from essential work partners to symbols of power and prestige, particularly after the advent of the automobile in 1866, which shifted the focus from utilitarian to entertainment purposes, notably racing. Horse racing itself boasts a rich history, with its origins tracing back to the ancient Olympic Games in Greece. It spread across nations, earning the moniker ‘Sport of Kings’ as medieval nobility showcased their prized steeds to potential buyers, cementing its status as one of the oldest forms of entertainment.

The Rise of American Horse Racing

In the United States, organized horse racing began around the 1660s in New York City on a 2-mile course in what is now Long Island. The 1800’s was a big decade for horse racing as it saw the founding of the three biggest horse races in the US, the Belmont Stakes (1867), the Preakness Stakes (1873) and the Kentucky Derby (1875). Additionally, the publication of the American Stud Book in the 1800s aimed to maintain breeding integrity and combat corruption within the industry. But as the popularity of horse racing has grown, so has the amount of prize money available to the winning horses, with this year’s Kentucky Derby champion bringing home $5M dollars. In retrospect, negating inflation, consider the fact that the purse in 1914 was a modest $10,000. As the stakes have increased on the horse racing circuit the amount of effort needed to win has also changed, forcing breeders and trainers to exercise every avenue to gain an advantage.

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In the realm of horse racing, where speed, stamina, and agility reign supreme, traditional breeding practices and pedigree analysis have long been the norm. However, the advent of genomics has revolutionized our understanding of the genetic foundations of performance traits in thoroughbred horses. Genomics offers a holistic view of an individual’s genetic makeup, providing insights into traits such as speed, endurance, and temperament. By analyzing the DNA of thoroughbreds, researchers can pinpoint specific genes associated with athletic prowess, enabling breeders to make informed decisions to optimize breeding programs. This technological advancement has led to the emergence of companies dedicated to engineering elite racehorses to produce the net triple crown winner.

The Genomics of Speed

At its core, genomics offers a comprehensive understanding of the genetic blueprint that underpins the traits and characteristics of an individual. In the context of horse racing, this translates to a deeper insight into the genetic factors that contribute to performance, health, and even temperament. By analyzing the DNA of thoroughbred horses, researchers can pinpoint specific genes associated with speed, endurance, and agility, allowing breeders to make informed decisions that optimize the breeding process. This technology has spawned a cottage industry of companies working to engineer the next triple crown winner.  Using the Thoroughbred as an example, the most valuable breed of horse in the world, has been a prized racehorse for centuries. Using a combination of breeding records and genetic analysis, researchers have shown that the Thoroughbred racehorse is from a mixture of Oriental (Arabian, Middle Eastern and North African) horses, as well as some native to the British Isles.   

One of the most significant breakthroughs in horse racing genetics lies in precision breeding, facilitated by the identification of genetic variations associated with athleticism. Traditionally, breeders relied on pedigree analysis and physical attributes to assess the potential of a racehorse, but with the introduction of the horse genome in 2007, researchers have identified over 25 million single nucleotide polymorphisms (SNPs). Subsequent genotyping studies were able to find unique variations tied to athleticism, 221 to be precise. Of these 221, one stood out among the crowd, myostatin (MSTN), and variations in this locus has been found to be highly predictive of potential for race aptitude in Thoroughbreds. Myostatin is a member of the transforming growth factor β family (TGF-β) that inhibits muscle growth by inhibiting the proliferation of muscle cells.  Sequence mutations found in the MSTN locus, found on chromosome 18, are reported to be the best predictors of thoroughbred performance. (SNP, g.66493737C/T) located in the first intron of the MSTN gene influences speed in the Thoroughbred and is the most promising candidate for optimum race distance. Population genetics studies also identified that homozygous C/C horses (American Quarter) are best suited to fast, short-distance, sprint races (1,000–1,600 m); heterozygous C/T horses compete favorably in middle-distance races (1,400–2,400 m); and homozygous T/T horses (Arabian) have greater stamina (>2,000 m). Additional GWAS studies focusing solely on horses that have the MSTN gene, and associated with lifetime earnings, have also linked 3 additional SNPs in the 3′ untranslated region of the MSTN gene, along with the insertion of a repetitive element (ERE-1) in the gene promoter.

The Origin of the Speed Allele

Breeding records for these horses go back hundreds of years and are considered on the most comprehensive records detailing ancestral relationships among domestic animal breeds. A group of researchers from Dublin, Ireland used these records, combined with genetic testing of historical museum samples, to piece together how the C-allele g.66493737 came into the thoroughbred gene pool. They found that 3 stallions imported from England in the late 17th and early 18th centuries can be traced paternally to all living thoroughbreds, meaning the gene pool has been kept intentionally small due to selective breeding. One of those stallions from the Darley Arabian sire line are related to 95% of living Thoroughbreds today. Using a pedigree-based approach they also discovered the single common ancestor for both the C and T cohorts, a horse born in 1935 named Nearco, considered one of the best racehorses and sires of the 20th century.

The evolution of the thoroughbred is intricately linked to the evolution of horse racing itself, with changes in racing practices influencing genetic distributions over time and across regions. The integration of genomics into horse racing genetics represents a new chapter in the pursuit of equine excellence, with the promise of producing a new generation of elite athletes. In today’s market, horses with the proper genotype are selling for >$1M as foals at auctions with the hope that they will one day become champions that command eye popping returns. Buyers are aided by genetic profiling provided by companies which claim to have identified markers linked to stamina, strength and energy use. Whether it’s the presence of genes associated with fast-twitch muscle fibers or superior cardiovascular endurance, genomics enables breeders to stack the proverbial genetic deck in favor of producing elite athletes. As we celebrate the ‘Fastest Two Minutes in Sports’ this weekend, let us raise a toast to the MSTN locus and the founding horses who paved the way for this exhilarating spectacle.

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