A bone-shortening gene mutation may have helped early Homo sapiens survive in extreme cold but may also be responsible for the debilitating osteoarthritis some of us suffer today.

Tens of thousands of years ago our early human ancestors moved north out of Africa into the much colder climates of Europe and Asia. As their surroundings and weather changed, survival of the fittest meant that adaptations to these changing conditions were passed on via genes that enhanced an individual's chance of survival.

After studying some of the genetic changes over the course of human evolution, scientists have found that a mutation in a gene called GDF5 was repeatedly favoured in the Homo sapiens that left Africa between 50,000 and 100,000 years ago.

To try to understand how this genetic change may have affected the human body at the time, researchers introduced the same gene mutation into mice and watched them develop over time. They found that the altered GDF5 gene led to the mice having reduced bone growth resulting in shorter limb length.


The question is - how could shorter bones have been advantageous for our ancestors? Researchers at Stanford University School of Medicine hypothesise that a more compact body structure could have been advantageous for helping us to withstand frostbite and reduce the risk of bone fractures from falling in icy conditions. In the animal kingdom many arctic mammals have small appendages, which minimise the amount of exposed surfaces from which heat can be lost.

Although this genetic mutation may have helped us to survive in extreme climates through the ages, research published this week in the journal Nature Genetics suggests that this mutated bone-shortening gene could also be increasing the likelihood of us developing osteoarthritis today.

Arthritis is the single greatest cause of disability in New Zealand, affecting one in six of us over the age of 15. Osteoarthritis starts with the cartilage in our joints becoming thin and uneven over time. As a degenerative disease that particularly affects the hands, feet, spine, hips and knees, osteoarthritis results in the tissues around our joints becoming painful and inflamed, eventually resulting in reduced joint motion and reduced mobility for the sufferer.

Previously, osteoarthritis was thought to be caused by wear-and-tear; however, this new research used a multidisciplinary team that combined the powerful approaches of developmental biology, evolutionary genomics and bioinformatics to show how osteoarthritis is connected to genetic factors as well as lifestyle.

Using data from the 1000 Genomes Project, which catalogued human genotype variation in 2504 individuals from 26 populations, this new study found that those of us carrying the GDF5 gene mutation are almost twice as likely to suffer from osteoarthritis during our lifetime. Aligning with the historical hypothesis, the mutation was also found to be prevalent in Europeans and Asians but rare among African populations.

Because osteoarthritis usually starts after the age of 40, it is likely that with their shorter life expectancies, our early ancestors didn't suffer from the disease before reproductive age and so the benefits of being shorter in colder conditions likely outweighed the risk of developing osteoarthritis later in life.

Currently there is no cure for osteoarthritis and sufferers are offered options to help treat their pain, or to replace whole joints with artificial implants. However, this new study combined with many more looking at variations in the human genome across thousands of individuals has the potential to open up new areas of treatment based on the molecular causes of arthritis.

While many of us are likely to experience the pain and discomfort that comes with osteoarthritis, perhaps in a small way we should be grateful that in doing so we are carrying the legacy of an ancient survival trait which may be the reason why we are here today.


Dr Michelle Dickinson, also known as Nanogirl, is an Auckland University nanotechnologist who is passionate about getting Kiwis hooked on science.
Tweet her your science questions @medickinson.