It may sound bizarre, and perhaps even a little scary on the surface, but we each receive approximately 60 new mutations from our parents. In general terms, we possess a lot more still; there are as many as 37 trillion cells in our bodies, which will undergo trillions of new mutations on a daily basis.
When we think of a mutation, we may not consider it as something human necessarily, but instead as something only really experienced by characters in comic books or films. The reality is that the majority of mutations pose no threat whatsoever to us, and there are even some that are enormously advantageous. To such a degree, in fact, that they are indeed comparable to superheroes.
We had a look at five human mutations, including:
- CCR5 and HIV resistance
- The PCSK9 gene and low cholesterol
- Adaptation at high altitude
and what they share with five comic book characters, and asked Patrick Short, Co-Founder and CEO at Sano Genetics, as well as Treated.com’s Clinical Lead Dr Daniel Atkinson, for their perspectives on the subject.
Tetrachromacy is a mutation thought to increase colour perception - and in some cases, bolster it dramatically. Scientists have estimated that it may allow certain tetrachromats to see 9 million more colours than the average individual. Additional cells in the eye, known as cones, allow for the enhanced colour visibility, with tetrachromats possessing four cones, rather than three. Besides blue, green and red cones, the fourth cone is highly responsive in the yellow-green region of the spectrum.
Because two X chromosomes are imperative to the development of tetrachromacy (as well as the anomalous gene), it’s highly likely that only women can experience it. The blue cone isn’t really integral to the mutation’s function as it’s not usually subject to any genetic errors. It’s also coded by a gene on a different chromosome - chromosome 7. In terms of the X chromosomes, however, women can carry the standard red and green genes on one of the X chromosomes and the anomalous gene on the other chromosome. As such (including the blue cone) there are four in total.
The number of tetrachromats who can see additional colours is unclear, but it’s estimated that 12% of women possess the gene .
The origins of tetrachromacy appear to lie in whether a woman has a father or son with mild colour blindness. The milder the son’s (or father’s) colour anomaly, the greater the possibility that the mother (or daughter) have the increased colour perception.
Comparable Superhero: Scott Summers, A.K.A Cyclops (from The X-Men)
Scott Summers, or Cyclops from The X-Men, probably bears the strongest resemblance to tetrachromacy. Cyclops, a divisive character amongst fans of the series, was also born with a mutation that gave him rare ocular abilities; specifically, the capacity to shoot optic blasts from his eyes potent enough to level mountains.
If you’re amongst the 1% of the European and US population to inherit the CCR5 delta 32 mutation from both parents, you’re 100 times less likely to develop HIV. The mutation works by deactivating the CCR5 receptor on white blood cells, which stops HIV from reaching the immune system.
It seems likely that a second patient overcame HIV having had a bone marrow transplant from an HIV resistant donor in March this year.
CCR5 is a shining example of genetic variation at its best, but also a clear reminder of the significance of mutations in bringing about progressive evolutionary change. As Treated.com Lead Dr Daniel Atkinson points out:
‘People might think that genetic mutations are worrying, and some of them are - localised mutations on a cellular level can sometimes lead to cancer or other health problems - but we should remember that the whole process of evolution depends on genetic mutations.’
Looking forwards, the CCR5 mutation could well be central to the continuous development of gene therapy and vaccines. It’s important to note however that it can’t offer protection from all strains of the HIV virus, such as CXCR4-tropic, which is capable of finding its way into the body via other receptors.
Maraviroc (also known as Selzentry or Celsentri), is a drug that can imitate the CCR5 mutation and subsequently provide some safeguarding against HIV, but daily consumption is currently imperative, with researchers still working on developing a form that doesn’t need to be taken as regularly.
Comparable Superhero: The Incredible Hulk (A.K.A Bruce Banner from The Incredible Hulk)
The Hulk’s exceptional ability to heal grants him total immunity to HIV and all other earthly viruses and diseases.
The Hulk’s immunity to HIV is referred to specifically in Issue 388 of the The Incredible Hulk comic book. Rick Jones, Banner’s current sidekick at the time, has cut his hand, and is very reluctant to take Banner’s former sidekick, Jim Wilson to hospital, in light of Wilson’s exposure to the HIV virus. The Hulk puts Jones’ fears to rest by taking responsibility for Wilson’s safe passage to hospital, explaining to him that his immune system will protect him from HIV.
Hyperthymesia, or Highly Superior Autobiographical Memory (HSAM), is a very rare mutation that massively refines memory retention and recollection. Neuroscience graduate Aurora LePort and neurobiologist Dr Craig Stark discovered that HSAM participants in their study possessed an accuracy of 87% when recalling autobiographical data or memories from periods of their lives long past. This figure is considered to far exceed the average individual’s recollective abilities.
Brain scans have revealed that there are differences in regions of the brain linked to autobiographical memory production amongst HSAM individuals, such as increases in the parahippocampal gyrus and the uncinate fascicle. This part of the brain plays a role in episodic memory retention.
Another contributing factor unearthed by LePort and Stark is the construction of mental systems amongst HSAM individuals, who seems to structure the brain in such a way that it can pinpoint very precise, previous experiences. For instance, putting memories in chronological order or in a categorical fashion (for example, every previous 15 April). It’s important to take into account the difficulty of substantiating these experiences however, with the use of dates the closest the study could get to legitimising such recall.
The quality and volume of autobiographical memories was put to the test in a 2016 study. LePort and a group of researchers compared a group of HSAM participants’ retrieval with other control groups. After one week, there were no differences, but beyond this point, the control groups’ recollection severely nosedived, whilst the HSAM group showed no sign of a decline whatsoever.
It remains speculative as to whether the HSAM population will provide a springboard for cures for Alzheimer’s and dementia, but the above research does give rise to the possibility that we all have access to memories of each day of our lives, but that we’re perhaps unable to tap into them because we just haven’t refined our retrieval, storage or retention capabilities enough.
Comparable Superhero (or villain in this case): Bane (from Batman)
Besides being highly intelligent and an exceptional strategist, Bane’s photographic memory has helped him to master as many as eight languages, whilst also making him a preeminent scientist. His memory is so lucid that it borders on total recall.
This gene prevents the liver from creating a protein called PCSK9, resulting in extremely low cholesterol levels, and a reduced chance of heart disease, for carriers of the mutation.
An absence of PCSK9 means that there is a larger volume of LDL-removal protein, which removes LDL cholesterol and as such there is less of it in the blood. One woman, who inherited the anomalous gene from both her mother and father, had an LDL reading of 14. This was an unprecedented case, and extraordinarily low, given that the figure in healthy adults is typically over 100 .
Further trials have produced similar findings; adults with one functional copy of PCSK9 and one mutation (approximately 2% of the study population) have been shown to possess a 40% reduction in cholesterol levels as compared to people carrying two functional copies of PCSK9 .
Putting this research into the context of heart disease, results have shown that participants with the inactivating PCSK9 gene are between 47% and 88% less likely to develop the condition . Indeed, these much lower cholesterol levels do not appear to have any damaging effects on the body whatsoever.
Comparable superhero: Wonder Woman (from Wonder Woman)
Perhaps unexpectedly, blood pressure plays a considerable part in the Wonder Woman comic series. Dr William Marston, writer of the Wonder Woman comics, helped to bring systolic blood pressure measurements into the mainstream. His research found expression in Wonder Woman’s use of blood pressure tests to tackle deception and espionage. When it seemed that someone was being dishonest, a baseline assessment for comparison was established - how that person looked when they were being sincere. This manifested as the Lasso of Truth, which Wonder Woman uses to draw out the truth from those subjected to the test.
How well we cope at high altitude very much depends on our red blood cell count. There is a gene prevalent amongst Tibetans that codes for a protein which is responsive to falling oxygen levels, allowing the population to thrive at 4,500 metres. Tibetans are able to prosper at high-altitude as a consequence of the mutation impacting on the body’s red blood cell count. The gene, known as EPAS1, is also associated with enhanced athletic and endurance abilities.
Present in 87% of Tibetan people , EPAS1 eradicates sickness, lethargy and other symptoms triggered by high altitude. Westerners, on average, usually start to experience ill effects due to the rise in red blood cells after two or three weeks, whereas the red blood cell count amongst Tibetans plateaus, meaning that adaptation is much easier.
The volume of oxygen in the blood amongst Tibetans actually drops in low-oxygen environments, putting less strain on the blood vessels and subsequently the heart.
The DNA for the EPAS1 gene dates back to human ancestry from between 30,000 and 50,000 years ago - the Denisovans . Evolution led to the gene being passed on, and enabled those Tibetans who settled on the Tibetan Plateau to grow accustomed to the environment. As Dr Atkinson explains:
‘Some genetic mutations can give certain organisms an advantage over their peers; these are then more likely to survive and reproduce and pass on the mutation meaning that, over time, a species evolves and adapts to its environment.’
Comparable Superhero: The Human Torch (from The Fantastic Four)
Jim Hammond, otherwise known as The Human Torch and part of the Fantastic Four, is also able to cope much better than the average person when oxygen levels are depleted. His ability to go into stasis, and ‘shut down’ his powers, enables him to survive until more oxygen is present.
Are we likely to see more beneficial human mutations emerge in the future?
Purely by virtue of natural selection, the number of mutations which are advantageous to us is only going to increase over time. Better access to genome sequencing (analysis of our DNA) will also help us to uncover more and more of them in the future.
‘There are so many amazing stories of human genetic variation leading to fascinating traits and adaptations. We are only scratching the surface of our understanding of the role of genetics in disease and human traits,’ notes Patrick Short.
‘As genome sequencing becomes more widely available, we are likely to find many more examples of protective genetic variants like PCSK9 that can greatly impact the way we treat disease.’
1. Newcastle University. Tetrachromacy Project: The Science.
2. Harvard University. A potential new weapon against heart disease: PCSK9 inhibitors. 2015.
3. Harvard University. A potential new weapon against heart disease: PCSK9 inhibitors. 2015.
4. Harvard University. A potential new weapon against heart disease: PCSK9 inhibitors. 2015.
5. The Guardian. Mutation in key gene allows Tibetans to thrive at high altitude. 2010.
6. BBC. How Tibetans survive life on the ‘roof of the world’. 2017.