Tag Archives: allele

We’ve identified a gene variant that seems to make people immune to the effects of COVID — but not to catching the virus

Researchers in the UK are closing in on a possible genetic defense against COVID-19. The findings could help explain why some people can catch the virus without getting sick.

A team of researchers led by members at the Newcastle University, UK, reports that the gene HLA-DRB1*04:01 likely confers its bearers some sort of protection against the coronavirus, or at least, from its more severe symptoms. This conclusion was drawn from the observation that the gene is found, on average, three times as often in asymptomatic patients compared to symptomatic ones.

The study worked with patients from the same communities in the UK in order to limit the influence of other factors such as environment, location, and socioeconomic status.

Genetically insulated

According to the authors, this is the first clear evidence of genetic resistance against COVID-19. While previous research has worked with whole genomes, that approach is far less effective than focusing on individual genes, as the current paper does. A genome-wide view can miss important tidbits of information, quite like watching the forest means you don’t focus on individual trees. The current research focused on comparing symptomatic to asymptomatic members of the same community to make it easier to spot how individual genes or alleles (variations of the same gene) can help protect us from COVID-19.

HLA-DRB1*04:01, a human leukocyte antigen gene, was identified as a prime candidate in this regard. The finding is based on samples taken from 49 patients with severe COVID-19 symptoms — who had been hospitalized with respiratory failure, — 69 hospital workers who had tested positive for the virus but were asymptomatic, and a control group.

These samples were analyzed so that the team could study the different HLA alleles present in the general population of North East England during the first lockdown. The asymptomatic patients, on average, were three times as likely to have the HLA-DRB1*04:01 allele in their genomes than symptomatic patients (16.7% vs. 5.1% after adjustment for age and sex).

From previous research, we know that the incidence of the HLA-DRB1*04:01 allele in the general population is directly correlated to latitude and longitude. People in the North and West of Europe are more likely to have this allele. Sadly, this also means that these areas will have a harder time keeping the virus under control.

“This is an important finding as it may explain why some people catch Covid but don’t get sick,” explains Dr. Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University, a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust, and co-author of the paper. “It could lead us to a genetic test which may indicate who we need to prioritize for future vaccinations.”

“At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don’t show symptoms, then they risk spreading the virus while asymptomatic.”

Populations of European descent, the authors add, are most likely to remain asymptomatic but still carry and transmit the disease to individuals that do not enjoy the same levels of genetic protection. The fact that there is a link between gene expression and geolocation is a well-established scientific concept. Genes are selected for by the unique sets of demands placed on different groups by their environment, so people living in different areas will evolve different types of genetic defences. The HLA gene is no different: they develop over generations as a response to pathogens.

“Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency,” adds co-author David Langton, whose company ExplantLab helped fund the study. “It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren’t aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.”

“This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area.”

Still, the team notes that more studies will be needed (both in the UK and other areas) as there may be different copies of the HLA genes providing resistance in other populations.

The paper “The influence of HLA genotype on the severity of COVID‐19 infection” has been published in the journal HLA.

Redheads do feel more pain — and they’re tougher than anyone else

The saying goes that redheads have more fun — but while that may be true, there’s also another side to that. Redheads feel more pain, studies have shown. At least, a different kind of pain.

Ed Sheeran is one of the world’s most famous redheads. I’m not sure what kind of pain he feels. Image credits: Eva Rinaldi.

Red hair occurs naturally in 1-2% of the human population, and it’s safe to say the world is fascinated with this particular hair color. To say that redheads have their own charm would be an understatement, but it has also had its downsides — particularly during the Dark Ages, when gingers were often considered witches or heretics.

It’s not clear why we’re so fascinated by them, but our fascination is about to go even deeper: due to their different genetic makeup, redheads require more anesthesia, are more prone to certain diseases, and experience pain differently.

The genetics of red hair

Red hair is most commonly found in the northern and western parts of Europe, especially in and around the British Isles. In Ireland, for instance, the population with red hair is estimated to be at around 10%, whereas in Scotland, around 6% of all people can boast that color. Still, even so, red is, by a wide margin, the rarest natural hair color.

Genetic studies have shown that a protein-coupled receptor called MC1R holds the key for this mutation. The MC1R protein is responsible for hair color, which can range from black or brown to lighter colors such as blonde and red. Most redheads have a recessive version of the MC1R gene.

The pigment also contributes to eye color. In addition, MC1R has also been reported to be involved in cancer (independent of skin coloration), developmental processes, and susceptibility to infections and pain.

It’s not a receptor that’s unique to humans. Similar studies have shown that some Neanderthals were redheads too, but we don’t really know if this mutation first emerged in Neanderthals or ancient humans. It’s possible that both humans and Neanderthals developed the trait separately.

Contrary to a popular belief, redheads are not disappearing. A 2007 report in The Courier-Mailwhich cited a National Geographic article and unnamed geneticists, claimed redheads were slowly disappearing. The story turned viral and became extremely popular. Many other websites picked up a similar story, quoting a study published in a magazine by the “Oxford Hair Foundation”. Well, turns out that the article was funded by hair-dye maker Procter & Gamble and was lacking in substance; to put it lightly. In truth, it was more a marketing stunt than a scientific article. The initial National Geographic article actually stated that “while redheads may decline, the potential for red isn’t going away.” For some reason, the idea just stuck — rest assured, redheads aren’t going anywhere. But back to our genetic makeup.

We know that at least some (probably most) of the genetic differences in redheads are associated with MC1R. Like most other cell surface receptors, MC1R is regulated by a set of complementary proteins. In 98% of the population, MC1R produces dark eumelanin, a dark type of pigment. But, in redheads, the mutation to MC1R leads to the production of a red pheomelanin, the pigment that gives the specific hair color. But it gets even more interesting.

The same mechanism that causes this red-tinged pigment also stimulates some hormones, including those called endorphins. Endorphins are secreted within the brain and nervous system and they have a whole bunch physiological functions — but they’re most famous for providing pain relief and making you feel some pleasure. Today, many geneticists are confident that the MC1R gene is directly related to pain.

A different kind of pain

Image credits: Luca Florio / Flickr.

A  number of studies have shown redheads feel pain differently and have different body reactions. For instance, one study found that people with red hair are more sensitive to thermal pain, while another showed that they are less sensitive to a wide array of painful stimuli, including electrically induced pain. So it’s not as simple as saying that redheads are more or less tolerant to pain — they just tend to feel pain differently. To make it even more intriguing, research has also shown that redheads require more anesthetic. Overall, they’re tougher than pretty much all other hair colors.

“…if you are walking down the street, there is nothing that you can see in somebody that will tell you how much anesthesia they need, except red hair,” says Daniel Sessler, who studied redheads’ resistance to anesthesia, finding that found that redheads require 19 percent more inhaled, general anesthesia than their dark-haired counterparts.

There’s no other genetic indicator of resistance to anesthesia, Sessler added — and it’s not just general anesthesia: localized anesthetics also seem to have a lower effect.

However, this is where things get interesting. While Sessler’s team has found that redheads are more sensitive to some types of pain (pain produced by hot or cold thermal shocks), other studies found that gingers are less sensitive to electric shock pain. This seems to strongly indicate that redheads process pain differently than other people, probably due to MCR1.

In other words, redheads do feel more pain, but they also feel less pain — they just process pain differently.

They’re also more resistant to pain produced by spicy foods, showing less sensitivity to capsaicin, the active component of chili peppers.

“Our tests showed that redheads are less sensitive to this particular type of pain. They react less to pressure close to the injected area, or to a pinprick. They seem to be a bit better protected, and that is a really interesting finding,” explains1` Professor Lars Arendt-Nielsen of the Center for Sensory-Motor Interaction at Aalborg University.

However, redheads also turned out to be more vulnerable to toothaches, and more afraid of the dentist (presumably due to the stronger pain they feel). Even more disturbingly, their genes make them more likely to suffer from several diseases, such as sclerosis.

There’s another interesting bit about redheads: they produce their own vitamin D, in much higher quantities than the rest of the population. Northern European countries have the highest concentrations of redheads, and there’s a very good reason for that. When humans migrated out of Africa, their skin color became lighter and lighter over time, as they were exposed to less sun. People who maintained darker skin lost the ability to naturally produce high levels of vitamin D, whereas people with lighter skin (especially redheads) didn’t. The ability is very useful in places like Scotland or Ireland, where sunshine can be a scarce commodity. This is also a downside because the light skin also means they’re more likely to get sunburns.

So, to sum up several studies, redheads:

  • are more vulnerable to extreme temperatures, especially cold;
  • are less responsive to anesthetic;
  • are less vulnerable to various types of pain, including electrical shocks;
  • are less responsive to spicy foods;
  • are more sensitive to painkillers;
  • produce more vitamin D naturally;
  • are more afraid of the dentist, and feel toothaches more strongly;
  • are at a greater risk of diseases such as sclerosis and endometriosis, as well as melanoma.

A widely believed myth claimed that redheads were more likely to bleed more heavily, up to the point where some surgeons refused to carry out complicated surgeries, due to a fear of excessive bleeding. That idea, however, is far less substantiated.

Tougher than others

Mary Magdalene is commonly portrayed with long red hair, as in this painting by Anthony Frederick Augustus Sandys. Image via Wiki Commons.

So, we do know that the same variants that give redheads their distinctive hair hue have significant other effects. In addition to these, some animal studies seem to indicate that redheads may react better to some drugs, and worse to others, compared with the general population. Hopefully, future studies can help us better understand these genetic differences, and help us tailor better custom treatments.

“It seems that MC1R is involved in central functions in the brain, and we know that subgroups like MC2R, MC3R and MC4R, which are also linked to redheads, have considerable involvement in brain functions. This could be the key to explaining why redheads are a little different to other people,” says Arendt-Nielsen.

There’s another important difference, which we have saved for fun. It seems that redheads do have more fun. A recent study found that redheads appear to have more sex than people with any other hair color. It’s not clear exactly why. It could be that they are just very rare (which can make them a sought-after prize), it could be that red hair just grabs your attention and serves as an advantage, or it could be that red is an indicator of youth and fertility.

At any rate, redheads exhibit a number of intriguing features. They feel more pain but are also more resistant to some types of pain, they are resistant to some conditions are more at risk from others. They draw our attention and often inspire us.

We may not understand the exact mechanisms which cause these differences, but for now, let’s just keep in mind that redheads are a bit different from most people. They’re certainly not witches, and they’re often tougher than the rest of us — but sometimes, they’re also more vulnerable.

Biologists discover new mutations which lead to asexuality

A team of evolutionary biologists at Indiana University has shown for the first time that asexual lineages of a species are doomed not necessarily from a long, slow accumulation of new mutations, but rather from fast gene conversions which unmask preexisting genetic mutations.

daphnia pulex

Copyright: Indiana University.

The groundbreaking research started with the sequencing of the entire genomes of 11 sexual and 11 asexual genotypes of Daphnia pulex – more commonly known as the water flea. This animal is used as a model for reproductive studies. The team discovered that every asexual organism shares common combinations of allelles (an alternative form of the same gene or the same genetic locus) for two different chromosomes transmitted by asexual males without recombination.

The whole thing spreads just like a contagious disease – although females become asexual, their sons need not be, and they spread the gene for asexuality further.

“One might think of this process as a transmissible asexual disease,” Lynch said. Exposure of pre-existing, deleterious alleles is, incidentally, a major cause of cancer, he added.

In the same study, they moved the age of the entire asexual radiation for D. pulex from millions of years to somewhere between 1.000 and 172.000 years. Some current asexual lines, Lynch explained, are only decades old.

“A pond of asexual daphnia may go extinct quite rapidly owing to these deleterious-gene-exposing processes, but the small chromosomal regions responsible for asexuality survive by jumping to new sexual populations where they again transform the local individuals to asexuality by repeated backcrossing,” Lynch said. “Soon after such a transformation, the processes of gene conversion and deletion restarts, thereby again exposing resident pre-existing mutations leading to another local extinction event. As far as the sexual populations are concerned, asexuality is infectious, spreading across vast geographic distances while undergoing no recombination.”

The team was also able to separate the genetic cause of asexuality – as it turns out, the entire line stems from a sister species, Daphnia pulicaria, possibly through a strange, unique hybridization event that brought the change.

“It is the contents of two non-recombining chromosomes derived from D. pulicaria that induce asexuality after male transmission of the otherwise asexual lineages,” Lynch said.