One Gene Change 2 Million Years Ago Left Humans Vulnerable to Heart Attack

     Scientists currently believe that humans are the only species to get heart attacks caused by clogged arteries. New research suggests that a single DNA change 2 million years ago is at the heart of this. Dr. James Jeffrey, a cardiologist, believes this finding creates the link between genetic and environmental factors which cause atherosclerosis and inflammation of arterial walls. However, even chimpanzees do not suffer from this affliction, meaning these types of heart attacks are specific to humans.

     To find out why researchers led by Dr. Nissi Varky and Dr. Amit Varky looked at a gene known as CMAH.  This gene functions by creating a sialic acid sugar molecule known as Neu5Gc. In other mammals a functioning version of this gene appears to greatly reduce the likelihood of atherosclerotic damage in blood vessels. The problem is this gene seems to have been switched off in humans roughly 2 to 3 million years ago. The researchers hypothesize that a dangerous malarial parasite thrived in the presence of Neu5Gc which forced the human genome to evolve and shut down production of this gene. While this change benefited humans by causing resistance to these parasites, it may have caused humans to become more vulnerable to develop fatty deposits in arteries.

      To test this theory, the team compared rates of atherosclerosis is mice with a working CMAH gene and a genetically modified version of the gene not producing Neu5Gc. This test showed that mice with the non-working gene showed nearly double the fatty buildup in their blood vessels. The mice without the gene were then fed red meat, which naturally contains New5Gc which caused even more significant buildup of fatty deposits in blood vessels.

        The researchers believe that this could be a reason that diets high in red meat are linked to heart disease. The hypothesize that contact with Neu5Gc sets off an immune response which leads to a chronic state of inflammation within the blood vessels. This gene may be the reason why people who don't eat meat altogether still are at a high risk for heart attacks while our other mammalian ancestors are not, Currently heart disease is one of the leading killers in the United States. If a form of gene therapy was developed to target this gene, and also other genes involved in how the body reacts to Neu5Gc, a very large dent could be made in the number of people who are claimed by heart disease, which is rapidly rising.





https://www.usnews.com/news/health-news/articles/2019-07-29/one-gene-change-2-million-years-ago-left-humans-vulnerable-to-heart-attack

Ancient Gene Mutation May Have Made Humans Well Equipped for Long-Distance Running

A new study that was published in Proceedings of the Royal Academy B proposes that due to a gene mutation that occurred millions of years ago, human beings all share an innate aptitude for long-distance running. The research was led by cellular and molecular physician Ajit Varki and his team. Their findings link the hominid transition from forest-dwellers to upright walkers of the African savannas straight to a gene called CMP-Neu5Ac Hydroxylase (CMAH for short).


Animals such as cows, mice, and chimpanzees carry a functional form of the CMAH gene. CMAH helps to produce the sugar molecule sialic acid, and all of these animals can produce two different types of the acid. Modern humans have a mutated form of this CMAH gene which causes it to be “broken”, and so they can only produce one type. In previous studies, this broken gene has been associated with severe muscular dystrophy, increased risks of cancer, and type II diabetes. However, Varki and others make the argument that its effects are not entirely negative, but that this mutated gene may have been what shaped humans into outstanding long-distance runners.


This gene mutated in our ancient ancestors about 2-3 million years ago. At this same time, these hominids were undergoing a change in their lifestyle in which their behavior became much more like modern humans and less primitive. Additionally, physiological changes were occurring – from larger feet, to strong gluteal muscles and long, powerful legs. These better adapted hominids were thus able to run for extremely long distances, enduring the brutal heat of the sun and exhaustion superior to the animals around them. This enabled them to practice the effective strategy of persistence hunting.


The physiological and behavioral changes can be seen quite clearly in one of our early ancestors – that of Homo erectus, “Upright man”, who lived between 1.89 million and 143,000 years ago. On the upper end, this widespread hominin was 6’1 and 150 pounds. While his brain was still somewhat smaller than ours, he was a quite intelligent and crafty survivalist. His body was built very similar to modern humans, with characteristic long legs and short arms relative to the torso that would have been well suited to endurance running. He would have very likely have acquired the CMAH gene mutation that we humans carry today.


To test their hypothesis, the research team subjected two groups of mice to run on small treadmills. One group had functioning CMAH genes, while the other had broken ones. The latter group was observed to have 30% greater endurance, ran 12% faster, and went 20% further than the mice with the functioning CMAH gene. After these tests, the mice’s muscles were analyzed by physiologist Ellen Breen, one of the co-authors of the study. She discovered that the mice with the mutated gene were better resistant to fatigue. Moreover, Jillian Mock of Popular Science stated that these mice were also able to process oxygen more efficiently.


Ultimately in their study, the team came to the conclusion that the CMAH mutation probably could have been key to hominids running faster and further. Nonetheless, as other scientists have pointed out, it is still too early to say for sure if the link between the mutated gene and human propensity for long-distance running exists, but future research should bring us closer to the answer.

Our Genetic Basis of Endurance Running

Humans have been long heralded for their ability to run for long distances, an ability that separates us from other mammalian species. As we learned from biodiversity and evolution, several key structural changes of early hominid species led to the development of humans being able to walk and run upright with ease. Some of these changes include: angled femoral bone head, s-shaped spine, and placement of foramen magnum directly under the skull. Although these structural changes have aided humans greatly in efficiently traveling on two legs, not much is known about the genetic mechanism of our endurance prowess. Not until a study done by Okerblom et al., did a genetic link to our long distance running ability was found.

The researchers pinpointed a mutated gene that they believed served as a catalyst to running, called CMAH, whose mutation coincided with a change in lifestyle from more primate to more human (2-3mya). Current mutations in CMAH have been most commonly linked with several disorders, such as muscular dystrophy and diabetes, however, Okerblom et al. hoped to shed light on the positives of this gene with their study. To conduct their study, the researchers utilized two groups of mice, one with and the other without mutations in the CMAH gene. To test the effects of mutation in this gene on endurance, they had the two groups of mice run on a small treadmill for a period of time. What they found was that the mice with the mutated version of the gene ran faster and further than the mice without mutations.

With the results of this study, Okerblom et al. sought to find the genetic basis of human's ability to run for long distances. Although several professionals advise caution in making an immediate link with the mutated CMAH gene to increased endurance, it is a promising step forward in finding an answer to our history of endurance.

As a distance runner myself, I often marvel at some of the athletic feats of elite distance runners when they smash a record at a certain distance. The record breaking marathon ran recently by Eliud Kipchoge at Berlin, for example, is one of the most impressive endurance feats I can think of. Eliud nearly clocked a sub two hour marathon, for a 4:38 average for each mile, which is faster than most of us can run for one. Eliud has been close to breaking two hours at this distance, which has long been thought to be impossible. That makes me wonder if he, in fact, carries a mutated version of the CMAH gene.

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