Gene linked to arthritis helped humans survive Ice Age

A gene linked to increased risk of osteoarthritis and reduced height may have helped early humans survive Ice Age, a study has found.

Researchers at the Stanford University and Harvard University in the US have shown that, despite its association with the painful joint disease, this genetic variant has been repeatedly favoured as early humans migrated out of Africa and into colder northern climates.

At least half of Europeans and Asians harbour the gene variant, which is relatively rare in African populations.

A more compact body structure due to shorter bones could have helped our ancestors better withstand frostbite and reduce the risk of bone fracture from falling, the researchers speculate.

These advantages in dealing with chilly temperatures and icy surfaces may have outweighed the threat of osteoarthritis, which usually occurs after prime reproductive age.

"The gene we are studying shows strong signatures of positive selection in many human populations," said David Kingsley, professor at Stanford.

"It is possible that climbing around in cold environments was enough of a risk factor to select for a protective variant even if it brought along an increase likelihood of an age-related disease like arthritis, which typically doesn't develop until late in life," he said.

The gene called GDF5 is involved in bone growth and joint formation, and mutations in the coding portion of the gene have been shown to cause malformations in leg-bone structure in mice.

In humans, GDF5 mutations are linked to shorter stature and joint problems; in particular, two nucleotide changes immediately upstream of the gene have been strongly associated with a 1.2 to 1.8-fold increase in the risk of osteoarthritis.

In the new study, researchers wanted to know more about how the DNA sequences surrounding GDF5 might affect the gene's expression.

Often, these noncoding sequences contain key regulatory regions known as promoters and enhancers.

Researchers were able to identify a previously unknown enhancer region they termed GROW1, which is several thousand nucleotides downstream of GDF5.

Further research showed that this nucleotide change has been repeatedly favoured during human evolution.

Modern humans migrated from Africa between 50,000 and 100,000 years ago. However, they were not the first to leave the continent. Neanderthals and Denisovans moved north into Europe and Asia about 600,000 years ago.

Researchers found that the same GROW1 variant was found in the DNA of both ancient and modern humans in Europe and Asia. However, the GDF5 variant that reduces bone length comes hand-in-hand with the two upstream nucleotide changes known to confer an increased risk for osteoarthritis.

"We've shown that positive evolutionary selection has given rise to one of the most common height variants and arthritis risk factors known in human populations," said Kingsley.