London, Aug 12 (HNA) – Neanderthals are often viewed as tough and resilient, enduring harsh weather conditions and facing off against dangerous prehistoric animals. But our extinct close relatives may actually have been highly sensitive to pain, according to a new study published on Current Biology. Researchers analyzed the DNA of three Neanderthal skeletons.
All contained mutations in a gene called SCN9A, which codes for a protein that controls how pain signals are sent to nerves in the spinal cord and brain.
The protein was more active in cells where these mutations were present, which would lower the threshold for feeling pain, Nature reports.
Modern British people who had inherited the Neanderthal mutations reported experiencing more pain in their lives, the team found. Neanderthal and human populations are thought to have mixed between 40,000 and 60,000 years ago.
Neanderthals and their Asian relatives, Denisovans, evolved largely separately from the ancestors of present-day humans for about 500,000 years. During that time, each group independently accumulated genetic changes that became frequent or fixed. However, late in their history, Neanderthals and Denisovans mixed with modern humans, which resulted in many genetic variants from Neanderthals and Denisovans being present in humans today.
As several Neanderthal genomes of high quality are now available, it is possible to identify genetic changes that occurred in many or most Neanderthals, investigate their physiological effects, and assess their consequences when they occur in people today.
Whereas most genetic differences between Neanderthals and modern humans that affect gene products occur singly in genes across the genome, genes that carry several such differences are of particular note.
One such case is the gene SCN9A, which encodes the Nav1.7 protein, a voltage-gated sodium channel in which all Neanderthal genomes sequenced to date carry three amino acid substitutions relative to modern humans: M932L; V991L; and D1908G. At these positions, extant monkeys and apes share the modern human residues. Nav1.7 is the only ion channel carrying amino acid substitutions in Neanderthals that is highly expressed in peripheral nerves mediating pain sensation.
The channel allows for the passage of sodium ions across the membranes of neurons in response to changes in electrical membrane potential. In humans, loss-of-function mutations of SCN9A cause insensitivity to pain and anosmia. Gain-of-function mutations, on the other hand, are a leading cause of idiopathic small-fiber neuropathy, where patients present with sensory symptoms and pain, with pain as the dominant symptom.
To investigate the electrophysiological effects of the three substitutions seen in Neanderthals, we synthesized genes encoding the modern human and Neanderthal versions of Nav1.7, transcribed these in vitro, and injected the mRNAs into Xenopus laevis oocytes. We chose this system, rather than, for example, cultured murine dorsal root ganglion cells, in order to test the effects of the three amino acid substitutions when expressed together with relevant human subunits, which differ from those of rodents by 5–47 amino acids.