Humans have entertained themselves with horse racing for hundreds of years. Even so, who would have guessed that some day the sport might help us understand how our blood pressure is regulated during exercise?

On June 17, researchers from the Swedish University of Agricultural Sciences in Uppsala reported discovering a DNA sequence in horses that underlies superior racing performance. The sequence influenced levels of two proteins involved in regulating blood pressure. Their results were published in the journal PLoS Genetics.

“By shedding light on the intricate mechanisms governing blood pressure modulation, the findings hold promise for advancing our understanding of cardiovascular health and disease,” the researchers wrote in their paper. They added that the implications also encompass “a myriad … physiological processes influenced by hormone signalling”.

Six years ago, the researchers had reported that horses with the genomic region ran faster. But at the time they couldn’t link the region to any underlying physiological trait. This has changed now.

Cold- and hot-blooded equines

The North Swedish draught horse is a sturdy breed people in the Nordic region use for farm and forestry work. It is ‘cold-blooded’, in this context meaning a large, heavy horse with an easy-going temperament. Faster, lighter, more energetic, and temperamentally more skittish horses are said to be ‘hot-blooded’. (The actual body temperature of all horses is 37.5-38.5 degrees C.)

By the early 1800s, people began to use the North Swedish horse in harness races, where the horse pulls a two-wheeled cart with a seat for the jockey. At first they used the farm horses, but inevitably, to gain a leg up, breeders began illegally crossbreeding the North Swedish horse with a hot-blooded American harness-racing breed called the standardbred.

Faced with this fait accompli, racing authorities divided the North Swedish into two new breeds: the North Swedish draught horse for farm work and the cold-blooded trotter for racing. Cold-blooded trotters share much of their genome with the North Swedish draught horse, but they also contain segments from the standardbred that enhance their racing ability.

The promoter and the enhancer

The horse genome has 32 chromosomes. Each chromosome is defined by a DNA molecule that runs throughout its length. Chromosomal proteins and RNA organise the DNA and regulate its expression.

Different cell types have different chromosomal proteins and RNA, but their DNA content remains constant. Each horse cell, like each human cell, contains two sets of the genome distributed in 64 chromosomes. One set is inherited from the father’s sperm and the other set from the mother’s egg.

The DNA molecule is like a ladder whose rails are made of a long series of alternating units of phosphate and deoxyribose (a sugar). Each deoxyribose unit is bonded to one of four chemical bases: adenosine (A), cytosine (C), guanine (G), and thymine (T). The As and Cs on one sugar-phosphate rail form hydrogen bonds with the Ts and Gs on the other, making up the DNA ladder’s rungs. The A-T and G-C base-pairs hold the two strands together as one large molecule.

In this way, each set of 32 chromosomes contains a little less than 3 billion base-pairs and code for just over 20,000 genes. Different horse breeds share much the same DNA sequence — just that about one in every few hundred base-pairs is different, giving rise to the breed’s variations.

A gene is a stretch of a few thousand base-pairs. A cell ‘reads’ this sequence as an instruction to make a specific protein. Next to the protein-coding sequence is another sequence called the promoter. The promoter allows the cell to express the relevant gene. Other sequences called enhancers, located tens to thousands of base-pairs away from the gene, influence the activity of nearby promoters.

These promoter-enhancer interactions influence gene expression in different types of cells.

The prize-money enhancer

The Swedish Trotting Association has recorded data about the racing performance of all competing horses, including the prize money earnt per race. The researchers collected DNA from blood and hair samples of 400 cold-blooded trotters that ran races between 2003 and 2015. In these DNA, they identified genes that both the cold-blooded trotters and the standardbreds shared but which trotters and draught horses didn’t.

Next, by examining the racing performance data, they found that trotters that had a sequence derived from standardbred horses on one or both copies of one chromosome performed much better in races and won more money.

This gene, associated with superior racing performance, had 5,564 base-pairs.  It was different from the ‘non-enhanced’ version by virtue of possessing different base-pair combinations in 14 positions on the DNA ladder.

When two DNA sequences are mostly identical and only a few base-pairs differ, the alternative versions are called haplotypes. Haplotypes are defined by listing the bases differing on one DNA strand.  The ‘élite’ and the ‘sub-élite’ haplotypes were respectively called EPH and SPH.

Effects on blood pressure genes

Trotters with the EPH haplotype had significantly lower blood pressure during and after exercise than trotters with the SPH haplotype. There was no difference before exercise, which suggested to the researchers that the EPH’s blood pressure regulation was related to exercise.

They also found the EPH haplotype decreased the levels of endothelin1 (EDN1) and increased the levels of endothelin3 (EDN3) — two proteins involved in regulating blood pressure — in the blood.

The EPH/SPH gene was located around 50,000 base-pairs away from the gene that made the EDN3 protein, so the researchers surmised the haplotype served as an enhancer.

That is, if the EPH and the SPH haplotypes enhanced the expression of the EDN3 expression in different ways, they could result in different blood pressure regulation pathways, leading to the differences in racing performance.

Taking the rough with the smooth

The researchers found the EPH/SPH haplotype gene was located in chromosome 22 in horse cells and in chromosome 20 in human cells. They conducted an experiment using human heart tissue to identify the promoters that interacted with the corresponding human sequence.

They found all the promoters that interacted with this sequence belonged to known blood pressure genes. Some of the proteins encoded by these genes also interacted with the EDN3 gene. Thus, the researchers were able to confirm the human counterpart of the horses’ ‘racing’ gene had a role in regulating blood pressure.

“These results are key to understanding the biological mechanisms behind blood pressure regulation in both human and horse elite athletic performance,” the researchers wrote in their paper.

Had the Nordic breeders been more scrupulous, they may not have allowed the EPH haplotype to be smuggled into the cold-blooded trotter’s genome. Had the race stewards been less scrupulous, corrupt practices such as doping or throwing the race might have made it harder to detect the superior performance because of EPH in the racing data. In this instance, the combination of human foibles and rectitude was just right.

D.P. Kasbekar is a retired scientist.

Finance Minister Nirmala Sitharaman speaks during a media briefing regarding the outcome of the 52nd Goods and Services Tax Council Meeting in New Delhi on October 7, 2023.
| Photo Credit: PTI

The Goods and Services Tax (GST) Council on Saturday lowered the tax rates on certain millet-based products, tweaked the age-related norms for members of the much-awaited GST Appellate Tribunals, and ceded the taxation rights on extra neutral alcohol to the States, while lifting the haze on several long-hanging issues.

The Council also signalled that there would be no back-pedaling on the 28% levy to be imposed on bets made in online gaming, casinos and horse racing from October 1, despite 13 States not having passed the enabling laws yet. Tax demands worth an estimated ₹1.5 lakh crore served on e-gaming firms for the prior period were also discussed, but it was asserted that the amended GST law is not retrospective in nature.

The notices issued to gaming firms for recovering taxes for the period up to September 30, were based on the law as it existed for betting activities, the Council was told when Ministers from Delhi and Chhattisgarh raised the issue. The Supreme Court is expected to take a view on the tax demands for the prior period on an appeal filed by the Revenue Department against a Karnataka High Court decision that dismissed a tax demand of over ₹21,000 crore served on Gameskraft.

18 States have amended laws

Union Finance Minister Nirmala Sitharaman said that Delhi’s Finance Minister had raised concerns about the impact on the gaming industry, while Goa’s Minister flagged the impact on casinos.

“The Delhi Minister’s concerns were more on the lines of, ‘taxing them [online gaming] will kill a sunrise industry, our youth needs this industry’, and also then taking up the issue of the notices that have gone to these companies. Of course, she also highlighted that this decision has been discussed over two to three years, and if the decision taken by the Council is going to hurt the young and youthful industry that has so much prospects, and so on,” she said.

Revenue Secretary Sanjay Malhotra said that at the latest count, 18 States had passed the necessary changes to their GST laws through ordinances or amendments to make the 28% gaming levy effective from October 1. Even the 13 States that have not passed it have said that they will pass it with effect from that date, he added.

GST cess

Asked if the recent trend of higher GST revenues could lead to swifter rationalisation of the GST rate structure, Ms. Sitharaman said this was not discussed in the Council, adding that no call has been taken on the rationalisation exercise yet. She parried a query on the reconstitution of a ministerial group tasked with the issue, which was earlier headed by former Karnataka Chief Minister B.S. Bommai.

The Council decided to meet in the future to work out a “perspective plan” on imposing a cess or surcharge on top of GST levies and how those surcharges could be used after March 2026, when the GST compensation cess used to recompense States for joining the indirect tax regime is expected to be phased out.

Rate rejigs

Meanwhile, the tax rates on some goods and services were clarified or tweaked, along with measures to facilitate trade and explicitly lay out procedures and tax treatment where confusion prevailed.

For instance, an emerging dispute on the treatment of guarantees issued by directors of companies for corporate loans has been settled by stating that they will not attract GST. Guarantees issued by companies to their subsidiaries will attract 18% GST on 1% of the guarantee offered, or the actual consideration, whichever is higher.

Taxpayers have also been granted an additional window till January 31, 2024 to file appeals against pending cases that were filed by the Revenue Department till March 2023, by paying a slightly higher proportion of the disputed tax levy as a “pre-deposit”.