Try to exceed one horse And you will probably lose. Despite the persistent myth that our species has evolved to hunt the prey of the savannah, Horses will usually beat Even the most elite human endurance athletes in speed and distance competitions. New research helps to explain why and how horses have a sporting advantage.
A study Posted March 27 in the newspaper Science finds that a unique and old series of Genetic mutations was the key to the evolution of the exceptional aerobic form of horses. Together, these changes allow horses to use oxygen quickly and effectively, without incurring cellular damage normally associated with burn through a lot of fuel.
“It really allows horses to take their cake and eat it too,” Gianni CastiglioneA co-author of the study and biologist at Vanderbilt University, says Popular science. Mutations partly explain why horses are able to maintain such a high proportion of muscles compared to their body mass, why they can maintain such a high concentration of mitochondria in their muscle cells, and why their maximum capacity to absorb and use oxygen (or their VO2 Max) is more than double that of a human athlete.
The resulting gene and protein in the center of adaptation are not only for horses – it also has serious clinical implications for health research. It is possible that by discovering the mystery of horses athletics, scientists can find new treatments for neurodegenerative diseases in humans such as Alzheimer’s disease or even therapies to block the decline of normal aging.
A first mutation of its kind in mammals
Castiglione and his team started their quest with a large study of genes through the tree of animal lifeIn search of how genetic sequences with known importance in people differ or remain the same in other species. Unexpectedly, they dressed on a specific equine alteration which helps to explain how horses (as well as zebras and donkeys) carry out their propulsive power. “We have found all this phenomenon in horses – something that we would never have predicted,” explains Castiglione.
Adding to the plot, the change of horses is closely linked to that which is also found in birds, says Elia DuhCo-author of the study and biomedical ophthalmologist and scientist at Johns Hopkins University. Castiglione and Duh published Previous research in 2020 On this avian discovery, and believe that change is an important part of the reasons why birds can fly, despite the way it is all energetic.
“This involved a convergent development,” explains Castiglione. But once scientists have dug more deeply, they found that genetic change in horses is much more complicated than bird mutation. It turns out that horses had to eliminate many more evolutionary obstacles to go to their final form. One of these obstacles is so rare, it is a type of mutation only before In a virus subset.
The protein factor
To understand how horses have found their athletic stride, it is first important to understand two proteins: NRF2 And Keap1. NRF2 is fundamentally identical to almost all vertebrates. It has antioxidant effects in the body, neutralizing the damaging molecules. He also plays a role in the production of the molecule Adenosine triphosphate (ATP), which is the energy currency of cells. Mitochondria alias The “power of the cell” burn ATP as fuel. The more ATP available, the more the work cells can do.
Although NRF2 is very important, it can also be deadly if it runs. In many vertebrates, hyperactive NRF2 triggers big problems such as tumor growth. “It’s a Goldilocks situation,” explains Castiglione. The animals “must regulate closely NRF2 and light it only when they need it.”
(In relation: Why study horses could also help humans stay healthy. ))
This is where Keap1 comes into play. He maintains NRF2 in check by sliding on NRF2 and obstructing his active site under normal cellular conditions. When enough oxidizing molecules, also called free radicals, appear to be an inevitable by-product Cells using energy, Keap1 is disabled. This releases NRF2 to fight free radicals and minimize cellular damage.
In birds, the modifications of the gene that codes for Keap1 make the protein non -functional. Avians have developed strategies to compensate for some of the consequences of having unregulated and constant active NRF2 proteins – while always rewarding the reward for sufficient energy to fly. “There is certainly a balance and – for different organisms – it is a question of optimal balance,” explains Duh.
Horses exploit the power to “recode”
Among horses and their close relatives, Things are a little more convoluted. The study authors found a single change of nucleotide from the start of the gene which code for Keap1, which would normally stop protein production. However, by sequencing proteins, cell cultivation experiences and comparisons with mouse and human, Duh and Castiglione cells have discovered that horses have no non -functional and slowed protein. Instead, the Keap1 equine version is even more sensitive to stress, and more sensitive to free radicals than the type that exists in other vertebrates.
Horses do this through a phenomenon called recoding. During recovery, a sequence of genes normally read as a sign of stop is translated into an amino acid which makes it possible to build the rest of the protein. A series of additional genetic changes had to arrive to allow recoding, but it is not clear if they came before or after the transfer of the Keap1 gene itself. Be that as it may, the resulting Keap1 protein is just enough different to offer advantages, without any obvious inconvenience.
This particular type of recoding was only documented before in virus that infects bacteria or bacteriophages. Finding the process in a vertebrate mammal reveals a whole new field of possible genetic oddity that is hidden in complex organisms. “It simply talks about the unique character of horses,” says Duh.
(In relation: Horses once had several hoof toes. ))
THE Pure number of DNA changes This must have taken place in quick succession to create this synchronous result also reflects the strong pressure that horses were probably below to become fast and tireless. The first horse -shaped animals were roughly the size of the dogs and faced several predators in their open habitat of meadows. To avoid being consumed at extinction, they have adapted. It was an “intense evolving crucible” and ancestral horses had to innovate to survive, suggests Castiglione.
It is not clear exactly when in the history of horses, these changes occurred. It could have been just before the origins of the genre Equalize 4 and 4.5 million years ago. Or, it was perhaps also distant that it is 55 million years ago, just after the The common ancestors of rhinos and contemporary horses separate. The genetic file is too incomplete to draw detailed conclusions on the chronology, note Castiglione. “We cannot deduce what happened once – unless you have a time machine. It is always a limitation with evolutionary work. ”
Future applications in humans
Despite the unanswered evolving questions, Castiglione and Duh believe that their results are solid enough to stimulate biomedical advances. Keap1 and NRF2 are crucial protein in many human diseases And aging. Knowing that one DNA nucleotide and an exchange of amino acids can considerably change the way in which the functions of the protein complex could be useful to approach some of the dysfunctions that appear.
Then there is the fact that horses have evolved a bypass solution to avoid being stuck with a poor quality Keap1 protein, despite a mutation that should have interrupted the production line. “In 10 to 15% of human diseases, you have a premature stop codon,” explains Castiglione. If the ancestors of horses found a means of producing a functional protein, a similar gene therapy inspired by equines could also be developed for humans.
However, for these future possibilities to materialize, there must be a continuous investment in exploratory and fundamental research, explains Castiglione. “All these works were funded by the National Institutes of Health),” he said Popular science. “It is because of their desire to finance fundamental research that we have now found things of clinical value that we could never have predicted.” Under the current administration, the NIH is Faced with major funding discounts.
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