Genetic mutation found that gives 1 in 5 ‘better resilience’ to cold


A fifth of the world’s population has a ‘superior resilience’ to colder temperatures thanks to a genetic mutation, allowing them to never feel the cold, study reveals. 

Researchers at Karolinska Institutet in Sweden had 32 healthy men aged 18 to 40 sit in 14 degrees Celsius water until their body temperature dropped to 35.5C.

They then measured the muscle electrical activity and took muscle biopsies of the volunteers to study their protein content and fibre composition.

The α-actinin-3 protein, found in ‘fast twitch fibres’ inside the muscles, is absent in 20% of people and its absence makes them better at maintaining temperature.  

These without the protein had more slow-twitch muscle fibres, suggesting the type of continuous, low intensity activation found in this alternative to the faster version of a muscle fibre is more energetically effective at generating heat.

This in turn allows the person without the protein to manage their heat more effectively than someone who has the protein and more ‘fast-twitch’ fibres. 

Researchers at Karolinska Institutet in Sweden had 32 healthy men aged 18 to 40 sit in 14 degrees Celsius water until their body temperature dropped to 35.5C. Stock image

The team behind the study believe this genetic variant may have protected modern humans against the cold as they migrated out of Africa over 50,000 years ago.

Protein α-actinin-3 is encoded in humans by the ACTN3 gene

The protein α-actinin-3, or Actinin alpha 3, has multiple roles in different cell types – but its expression is limited to skeletal muscle.

It is found only in fast-twitch fibres and is absent in almost 20 per cent of people – almost 1.5 billion individuals.

This absence is due to a mutation in the gene that codes for it. 

The ACTN3 gene encodes for the  protein and in sports circles has been known as the ‘gene for speed’ due to its link to muscle fibres. 

Recent studies found a link between the absence of the protein and higher cold tolerance. 

Based on their study, the team believe that about 1.5 billion people worldwide will carry the variant today – increasing their tolerance of colder climates. 

Co-senior author Håkan Westerblad said: ‘Our study shows an improved cold tolerance in people lacking α-actinin-3, which would have been an evolutionary survival advantage when moving to colder climates.

‘Our study also highlights the great importance of skeletal muscle as a heat generator in humans.’ 

The findings suggest this is because the deficiency of α-actinin-3 boosts cold tolerance by increasing their muscle tone and leads to more slow-twitch muscles.

When immersed in cold water during an experiment, people with the variant had an increase in muscle tone rather than shivering.

The loss of α-actinin-3 is caused by the loss-of-function (LOF) variant of the ACTN3 gene and became more common as more humans moved to colder environments.

Around 1.5 billion people worldwide carry the ACTN3 LOF variant today and therefore lack α-actinin-3.

Although this protein deficiency is not linked with muscle disease, it does impair performance during power and sprint activities.  

The change became more prominent as humans began to move into cooler climates – which researchers use as their argument why it may improve cold tolerance. 

To test this idea, the team immersed 42 healthy 18 to 40-year-old men with either the LOF variant or functioning ACTN3 in 14 °C water.

The men remained in the water for 20-minute periods, broken up by ten minute pauses in room-temperature air.

Cold-water exposure was continued until the rectal temperature reached 35.5 degrees, or for a total of two hours plus fifty minutes of pauses.

Of those men that had the genetic variant 7 out of 10 where are able to maintain their body temperature above 35.5°C for the complete cold water exposure period.

However, only three and 10 of those without the variant were able to do so. 

The muscles of people without the protein contain a greater proportion of slow-twitch fibres, which allows them to maintain their body temperature in cold environments in a more energy-efficient way

The muscles of people without the protein contain a greater proportion of slow-twitch fibres, which allows them to maintain their body temperature in cold environments in a more energy-efficient way

MUSCLES: AN INTRICATE NETWORK OF SINEWS THAT FORM IN THE BODY

Muscles form an intricate network of sinews throughout the body of animals. 

They respond to electrical stimulation which is carried from the brain to the muscle via nerves. 

There are different types of muscle, which are often made of different types of tissue. 

For example, the heart, which never stops beating, is made of a different material to skeletal muscle.

Skeletal muscle is attached to one end of a bone. It stretches all the way across a joint (the place where two bones meet) and then attaches again to another bone. 

Skeletal muscles are held to the bones with tendons.

Once the electrical signal reaches the muscle it triggers a contraction. 

This is done by two types of protein overlapping and working against each other. 

A thick filament composed of the protein myosin and a thin filament composed of the protein actin. 

Muscle contraction occurs when these filaments slide over one another in a series of repetitive events. 

On average, loss of α-actinin-3 resulted in half the rate of temperature decline in the rectum and on the calf muscle.

People with the variant also showed a shift toward more slow-twitch muscle fibres, causing an increase in muscle tone rather than shivering during immersion. 

By contrast, individuals without the variant had more fast-twitch muscle fibres, which doubled the rate of high-intensity bursting activity.

The superior cold resistance of people with the variant was not accompanied by an increase in energy consumption.

This suggests that the continuous, low-intensity activation of slow-twitch muscle fibres is an energetically effective way to generate heat.

Results in mice showed that α-actinin-3 deficiency does not increase cold-induced brown fat tissue, which generates heat in hibernating mammals and human infants.

Co-senior study author Professor Marius Brazaitis, of Lithuanian Sports University in Kaunas, Lithuania, added: ‘Although there are many avenues for future investigation, our results increase our understanding of evolutionary aspects of human migration.

‘While the energetically efficient heat generation in people lacking α-actinin-3 would have been an advantage when moving to colder climates, it might actually be a disadvantage in modern societies,’ he said. 

Housing including Nico protection less important and as we’ve got relatively limited access to food such energy efficiency and our bodies can actually result in obesity Type II diabetes and other metabolic disorders, Brazaitis added. 

For now, it remains uncertain whether the loss of α-actinin-3 affects brown fat tissue or cold tolerance of human infants, whose survival would have been an important factor during the human migration to colder environments.

While the variant may increase slow-twitch muscle fibres at birth, it is possible that this shift doesn’t occur until later in life.

Researchers add it is also not clear whether α-actinin-3 deficiency affects heat tolerance or responses to different types of athletic training. 

The findings have been published in the American Journal of Human Genetics. 

DNA AND GENOME STUDIES USED TO CAPTURE OUR GENETIC PAST

Four major studies in recent times have changed the way we view our  ancestral history.

The Simons Genome Diversity Project study

After analysing DNA from 142 populations around the world, the researchers conclude that all modern humans living today can trace their ancestry back to a single group that emerged in Africa 200,000 years ago.

They also found that all non-Africans appear to be descended from a single group that split from the ancestors of African hunter gatherers around 130,000 years ago.

The study also shows how humans appear to have formed isolated groups within Africa with populations on the continent separating from each other.

The KhoeSan in south Africa for example separated from the Yoruba in Nigeria around 87,000 years ago while the Mbuti split from the Yoruba 56,000 years ago.

The Estonian Biocentre Human Genome Diversity Panel study

This examined 483 genomes from 148 populations around the world to examine the expansion of Homo sapiens out of Africa.

They found that indigenous populations in modern Papua New Guinea owe two percent of their genomes to a now extinct group of Homo sapiens.

This suggests there was a distinct wave of human migration out of Africa around 120,000 years ago.

The Aboriginal Australian study

Using genomes from 83 Aboriginal Australians and 25 Papuans from New Guinea, this study examined the genetic origins of these early Pacific populations.

These groups are thought to have descended from some of the first humans to have left Africa and has raised questions about whether their ancestors were from an earlier wave of migration than the rest of Eurasia.

The new study found that the ancestors of modern Aboriginal Australians and Papuans split from Europeans and Asians around 58,000 years ago following a single migration out of Africa.

These two populations themselves later diverged around 37,000 years ago, long before the physical separation of Australia and New Guinea some 10,000 years ago.

The Climate Modelling study

Researchers from the University of Hawaii at Mānoa used one of the first integrated climate-human migration computer models to re-create the spread of Homo sapiens over the past 125,000 years.

The model simulates ice-ages, abrupt climate change and captures the arrival times of Homo sapiens in the Eastern Mediterranean, Arabian Peninsula, Southern China, and Australia in close agreement with paleoclimate reconstructions and fossil and archaeological evidence.

The found that it appears modern humans first left Africa 100,000 years ago in a series of slow-paced migration waves.

They estimate that Homo sapiens first arrived in southern Europe around 80,000-90,000 years ago, far earlier than previously believed.

The results challenge traditional models that suggest there was a single exodus out of Africa around 60,000 years ago.

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