Can a genetic change make you superhuman?

Kitty Pryde, the iconic X-Woman from Marvel Comics, once said: “We are mutants. Born different from baseline humanity, with an enhanced genome that gives us super-powers.” All fiction draws on elements of reality, and as surprising as it might sound, there are genetic changes in the human DNA that have been linked with superpowers.

The mysterious book of life

The Human Genome, our complete set of DNA, is the “book of life” that contains the instructions for the human body to develop, survive, and reproduce. In this book, words, sentences, paragraphs, and chapters are formed with only the 4 letters that make up our whole DNA: A, C, T, G.

• The 4 letters that make up the whole book are known as ‘nitrogen bases’. Specifically, these four nitrogen bases are adenine (A), cytosine (C), thymine (T), guanine (G). The DNA molecule consists of two strands connected by hydrogen bonds between the nitrogen bases of each strand. Thus, nitrogen bases are the structural foundation of the DNA molecule.

• Specific words that make up the order of a sentence are the ‘introns’ and ‘exons’. Exons are necessary for protein synthesis. In contrast, introns, the non-coding regions of the DNA, are important for gene regulation.

• A specific arrangement of words makes the sentences within the DNA book, with each sentence carrying a particular meaning. These are referred to as genes. Genes are specific sections of DNA that contain precise information on how to build proteins required in the human body.

• Proteins, the workhorses of cells, can be compared to paragraphs, with each paragraph serving a distinct purpose or function.

• Expanding further, chapters can be related to chromosomes. Just as chapters group related content, chromosomes organize genes and genetic material in a similar manner.

• Last but not least, we have the font. The font can be correlated to ‘alleles’. Alleles are different forms of the same gene. In humans, they are arranged in pairs, with one allele inherited from each parent. These alleles are located on the same part of the chromosome and influence an individual’s genetic traits, such as eye color.

Any change in the words or sentences of the ‘Genome Book’, whether it was there in the manuscript before the book was printed (germline) or manifested later (acquired) in the circulated copy, is referred to as a mutation, a variant, or a genetic change. When a genetic change occurs but is common in the population at a frequency of 1% or more, it is called a polymorphism [1]. Just like a change in a book can be a typo or change the entire meaning of a word and the subsequent text, mutations can be harmless or harmful, and in rare cases, even beneficial [2]. In this blog article, we will explore some beneficial mutations that can occur in humans giving them superpowers and making them exceptionally unique.

Superpower genes

More than a ‘speed’ gene

When we talk about speed, the first person who comes to mind is the world’s fastest human, Jamaican sprinter Usain Bolt. Can genetics be one of the reasons he is so fast, or that some of us run faster than others can? All of us have a gene called ACTN3 that provides instructions for creating a protein responsible for the fast-twitching of muscle fibers, enabling us to run [3]. ACTN3 gene-specific polymorphisms can influence our athletic prowess and sports performance by controlling the type and quantity of muscle fibers we possess. A common polymorphism, R577X, in the ACTN3 gene, determines whether an individual carries the R allele, associated with the production of the protein, or the X allele, linked to the absence of the protein. A multi-cohort study in a performance-homogenous group of elite sprinters revealed that in a group of individuals, the most common genotype was the RR, confirming that individuals with the R allele (RR genotype) have greater sprinting predisposition. However, individuals with the X allele (XX genotype) exhibited higher endurance in long-distance running [4]. It is noteworthy to mention that another study showed that the XX genotype had a low frequency in elite Jamaican and African-American sprinters, providing evidence that they are well-suited for sprint performance [5]. Apart from speed and endurance, the R577X polymorphism also affects exercise adaption, exercise recovery, and the risk of exercise-associated injury [6].

The Hercules gene

The Greek Mythology hero, Hercules, had incredible, godlike strength; he was strong enough to carry the world on his shoulders! Today, an increasing number of people spend many hours in the gym aspiring to herculean strength. However, in individuals with the K153R polymorphism in the MSTN gene, prominent muscle mass develops naturally from a very early age without any training. The K153R polymorphism acts as a genetic “brake” on the production or activity of myostatin, which plays a crucial role in regulating muscle growth and development [7]. Consequently, there is a continuous signal for muscle cells to grow and proliferate. Individuals with the polymorphism have a rare condition called myostatin-related muscle hypertrophy characterized by impressive muscle development and strength and usually identified at birth or during infancy [8]. The condition can be diagnosed during a physical exam by visually assessing the individual’s muscle mass, by ultrasound to determine the cross-sectional plane length of the quadriceps femoris muscle as it tends to be higher than the average [8], and by genetic testing that looks for mutations in the MSTN gene. Although there is no treatment, the condition is not painful, and it is unrelated to any medical complications or clinical symptoms [8].

The unbreakable bones gene

The LRP5 gene produces a protein that regulates bone density and strength. Mutations in the LRP5 gene can have an impact on an individual’s bone health. While some LRP5 mutations affect bone density and are associated with conditions like osteosclerosis and osteoporosis [9], the G171V mutation causes increased bone mineral density, resulting in unusually strong and thick bones with high resistance to fractures. Individuals with this mutation may not have obvious clinical symptoms but sometimes can have bone swellings that appear in the palate, or neurological complications including deafness and sensorimotor neuropathy [10, 11].

Pain insensitivity genes

Pain sensation is an individual’s protective weapon and a way of warning about danger. Pain evaluation also helps doctors assess how pain affects a patient and reach a diagnosis. While exceptionally rare, people affected by congenital insensitivity to pain (CIP) cannot feel any pain [12]. Imagine getting hurt and not being able to feel it! While fascinating, it can also be dangerous, as patients who cannot feel pain may be inadvertently injured without noticing, and may be more prone to accidents or health issues [13]. CIP is caused by genetic mutations in specific genes. Some of these genes are:

SCN9A gene

The main function of the SCN9A gene is to facilitate the transmission of pain signals, through the sodium channel Nav1.7, from nerve cells to the brain [14]. Specific mutations in the SCN9A gene can cause channelopathy-associated insensitivity to physical pain. These mutations lead to the production of a non-functional subunit of the Nav1.7 sodium channel, which blocks the opening of the channel, limiting sodium ions from entering the nociceptors. As a result, the nociceptors are unable to transmit pain signals from an injured site to the brain [15].

FAAH gene

The FAAH gene encodes the FAAH protein that is involved in breaking down anandamide, which is called the “bliss molecule” for the role it plays in producing feelings of happiness and mental wellness by binding to cannabinoid receptors in the brain and body [16]. In a single patient, scientists found that a single-nucleotide polymorphism in the FAAH gene can reduce the function of the FAAH protein, thereby increasing anandamide levels, resulting in pain insensitivity and lower anxiety [17]. In addition to the FAAH polymorphism, a microdeletion to a nearby pseudogene, called FAAH-OUT, was also present and thought to be associated with changing the brain’s interpretation of pain signals [17]. Pseudogenes are DNA sequences that resemble genes but cannot code for a protein. However, pseudogenes can regulate coding genes through some pathways [18].

PRDM12 gene

One of the main functions of the PRDM12 gene is pain perception [19]. It is established that the PRDM12 gene modulates the nerve-growth factor (NGF) pathway, which sensitizes nociceptors. Nociceptors are sensory receptors that send signals to the spinal cord and brain when there is a “possible threat” [20]. Mutations in this gene can cause pain insensitivity because of a lower NGF expression. Most of these mutations are related to a rare genetic condition called hereditary sensory and autonomic neuropathy (HSAN). The clinical symptoms vary including the inability to sweat (anhidrosis), induced self-injuries, oral and growth delays. Diagnosis of HSAN is based on clinical examination, but as symptoms differ, genetic testing can make a definite diagnosis and lead to early treatment and interventions [21].

The sleepless gene

In the busy world we live in, sleep helps us relax and allows our body and mind to rejuvenate. It is also essential for many vital functions that keep us healthy, such as growth, energy conservation, modulation of immunological responses, and release of hormones. To function optimally, it is recommended to sleep approximately 8 hours a day [22]. However, some people can sleep very few hours and be productive, functional, and healthy. One possible explanation for this is the P384R mutation in a gene called DEC2, which controls the levels of orexin, a hormone that modulates arousal and wakefulness and regulates the circadian rhythm [23, 24].

Recently, another mutation in the ADRB1 gene, which is related to short sleep, was also discovered [25]. While short-sleep individuals who don’t have the mutation are more likely to experience various types of health problems such as heart attacks and type 2 diabetes, individuals with the DEC2 and ADRB1 gene mutations seem to be protected from adverse health consequences despite their limited sleep hours [26].

Therapeutic approaches

Apart from being fascinating, ‘superpower mutations’ can open new avenues of research into finding therapies for specific disorders. By trying to study and understand these mutations, scientists hope to utilize them, or their mechanism of action, into beneficial therapeutic approaches through gene editing. Gene editing is a method to modify specific regions of the DNA of living organisms. Some noteworthy approaches exploiting superpower mutations to prevent, treat, or cure certain disorders:

Reducing or blocking pain by targeting CIP-related genes

People who suffer from chronic pain and cancer patients with chemotherapy-induced neuropathy would benefit immensely from new, safe, and effective pain treatments. During the last few years, scientists have been trying to develop targeted SCN9A gene and Nav1.7 channel pain therapies to reduce the function of Nav1.7 sodium channel akin to specific SCN9A gene mutations. However, small molecules that directly target the sodium channel have not been clinically successful [27]. A recent study has shown that a targeted Nav1.7 gene therapy, reducing Nav1.7 function, could be a treatment for chronic neuropathic pain [28]. This study highlights the potential of gene therapies as promising and viable alternatives to current pain treatments, but further research is needed.

Modulating LPR5 mutations for bone disorders

As previously mentioned, LPR5 mutations cause conditions of two extremes: increased bone fragility and low bone mass, or increased bone mass, with the G171V mutation being the prime example of the latter. While extensive research is still warranted, it is interesting to note that transgenic mice expressing the G171V mutation have demonstrated that the increased bone mineral density was caused by an increased number of active osteoblasts, underscoring the possible utility of LRP5 polymorphisms as targets for therapies for bone disorders [29, 30].

Myostatin inhibition for disorders affecting muscles

Myostatin normally limits the muscles’ growth and development throughout the body to make sure that the muscles grow normally. Certain disorders, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), affect the muscles and make them weak because of the higher levels of myostatin. Reducing the production of myostatin has clinical benefits [31]. While this is currently achieved through myostatin inhibitors, it is probable that the K153R polymorphism mentioned above is a research area worth exploring.

Conclusion

By decoding the human genetic code, we can uncover an increasing number of genes and gene mutations that determine our genetic identity and shape our lives and everyday activities. While they sound scary, we must keep in mind that mutations are not always harmful and do not always lead to genetic disorders, cancer, or detrimental consequences. Some mutations can even prove to be beneficial. Since the beginning of time, mutations have been the driving force behind evolution: they generate genetic diversity and enable populations to adapt to changing conditions. Already, some remarkable genetic mutations that grant extraordinary powers have been identified. These mutations not only can make individuals feel superhuman but also hold promise for scientific research aimed at finding treatments through gene editing techniques.

The content of this article is for informational purposes and is not intended to replace medical advice. Please visit your healthcare provider if you have concerns about your health and well-being.

References

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