Tag: Neanderthals

Neanderthal Gene Variants Associated with Greater Sensitivity to Some Types of Pain

Source: Pixabay CC0

People who carry three gene variants that have bene inherited from Neanderthals are more sensitive to some types of pain, according to a new study co-led by UCL researchers. The findings, published in Communications Biology, are the latest findings to show how past interbreeding with Neanderthals has influenced the genetics of modern humans.

The researchers found that people carrying three so-called Neanderthal variants in the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.

Previous research has identified three variations in the SCN9A gene – known as M932L, V991L, and D1908G – in sequenced Neanderthal genomes and reports of greater pain sensitivity among humans carrying all three variants. However, prior to this study the specific sensory responses affected by these variants was unclear.

An international team measured the pain thresholds of 1963 people from Colombia in response to a range of stimuli.

The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.

The authors found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure. Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.

When they analysed the genomic region including SCN9A using genetic data from 5971 people from Brazil, Chile, Colombia, Mexico and Peru, the authors found that the three Neanderthal variants were more common in populations with higher proportions of Native American ancestry, such as the Peruvian population, in which the average proportion of Native American ancestry was 66%.

The authors propose that the Neanderthal variants may sensitise sensory neurons by altering the threshold at which a nerve impulse is generated. They speculate that the variants may be more common in populations with higher proportions of Native American ancestry as a result of random chance and population bottlenecks that occurred during the initial occupation of the Americas. Although acute pain can moderate behaviour and prevent further injury, the scientists that say additional research is needed to determine whether carrying these variants and having greater pain sensitivity may have been advantageous during human evolution.

Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.

Previous research by co-corresponding author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) has shown that humans also inherited some genetic material from Neanderthals affecting the shape of our noses.

Dr Adhikari commented: “In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago.

“Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm. Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous.”

First author Dr Pierre Faux (Aix-Marseille University and University of Toulouse) said: “We have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from the Neanderthals. But genes are just one of many factors, including environment, past experience, and psychological factors, which influence pain.”

Source: University College London

Neanderthal Genetic Influences on Human Immune System and Metabolism

Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.

Neanderthal genes comprise some 1 to 4% of the genome of present-day humans whose ancestors migrated out of Africa, and new research has shown that their lingering presence shapes the immune systems and metabolism of people of non-African ancestry. Some of these genetics changes are detrimental, but are slowly being replaced by human versions.

A multi-institution research team including Cornell University has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals that took place some 50 000 years ago. (The study applies only to descendants of those who migrated from Africa before Neanderthals died out, and in particular, those of European ancestry.)

In a study published in eLife, the researchers reported that some Neanderthal genes are responsible for certain traits in modern humans, including several with a significant influence on the immune system. Overall, however, the study shows that modern human genes are winning out over successive generations.

“Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors’ migration out of Africa,” said study co-lead author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. “We have made our custom software available for free download and use by anyone interested in further research.”

Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300 000 British people of non-African ancestry, the researchers analysed more than 235 000 genetic variants likely to have originated from Neanderthals. They found that 4303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person’s natural immune resistance to certain diseases.

Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.

While the study used a dataset of almost exclusively white individuals living in the United Kingdom, the new computational methods developed by the team could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans’ genetic influences on modern humans.

“For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks,” said senior investigator Sriram Sankararaman, an associate professor at the University of California, Los Angeles. “More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences.”

Source: Cornell University

Medicine Nobel Prize Awarded to Neanderthal DNA Scientist

Genetics
Image source: Pixabay

This year’s Nobel Prize in Physiology or Medicine has been awarded to evolutionary scientist Professor Svante Pääbo, “for his discoveries concerning the genome of extinct hominins and human evolution”.

As explained by the Nobel Assembly at Karolinska Institutet: “Through his pioneering research, Svante Pääbo achieved something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova.” Prof Pääbo further made the important discovery that cross-breeding occurred between Homo sapiens and our extinct relatives after the migration out of Africa some 70 000 years ago. The gene transfers from extinct hominins that have left traces among present-day humans outside Africa have proven physiologically significant, for example, for human resistance to infections.

Prof Pääbo received a doctorate in medicine in 1986 from Uppsala University. He has returned several times to the University as visiting professor and has also been a member of the University Board.

Uppsala University Vice-Chancellor Anders Hagfeldt thinks Prof Pääbo is an excellent and pleasing choice.

“His research identifying and mapping human origins is tremendously fascinating and of course it’s very pleasing that he is connected with Uppsala. I’m sure many people at the University are as happy as I am today, we have many fine researchers following in his footsteps,” he said.

Mattias Jakobsson, professor at the Department of Organismal Biology, who is also engaged in research on human evolution, had thought that ProfPääbo was bound to win the prize sooner or later, though his name had not been mentioned much this year.

“It’s fantastic, both for him and for the entire field of research. And it’s very appropriate that it’s the prize in medicine, his latest work has focused on patterns of genetic variation due to our Neanderthal heritage. Some of these patterns relate to COVID, for example,” he said.

Source: Uppsala University