How they survived an ice age

Genetic mutation that left them shorter and increased osteoarthritis risk might have kept them alive

Shortness, reduced mobility and sore joints may not come to mind when you think of survival of the fittest. But human evolution could suggest otherwise.

In a new study, researchers found that as early humans migrated into colder northern climates, a genetic mutation that knocks about a centimetre off height and increases the risk of osteoarthritis by up to 80 percent may have helped some of them survive the most recent ice age.

While some traits resulting from this mutation may seem unfavourable today, they were advantageous to early humans venturing out of Africa about 60,000 years ago.

“There are many cases like this where evolution is a trade-off,” said David Kingsley, an author of the study, which appeared in Nature Genetics on Monday, and a professor of developmental biology at Stanford University.

The shorter stature may have helped these prehistoric humans retain heat and stave off frostbite in their extremities, the authors said. It also may have reduced their risk of life-threatening bone fractures when slipping on icy surfaces. But the same gene puts humans at greater risk for arthritis in the modern era as they live well beyond their reproductive years.

The study looked at variants of the GDF5 gene, which was first linked to skeletal growth in the early 1990s, and is known to be involved in bone growth and joint formation. The researchers wanted to understand how the DNA sequences around it might affect the gene’s expression, focusing on one region they named GROW1.

After analysing the sequence of GROW1 in the 1,000 Genomes Projectdatabase, a collection of sequences from human populations around the globe, the researchers identified a change in one nucleotide, the basic building block of DNA. The change is prevalent in Europeans and Asians but rare in Africans. To see if that mutation was incidental or actually caused shorter stature, they tested the nucleotide change in mice and found it decreased the length of their long bones, much as it is thought to do in humans.

That mutation of the regulatory region analysed in the study is present in more than 50 per cent of the population in Europe and Asia. In some Asian populations, it’s up to 90 per cent, Kingsley said. Even if the variant plays only a small role in increasing arthritis risk, the sheer number of people who possess it means it can have a significant effect.

“The very abundance of the change means it could contribute to a lot of cases of arthritis,” Kingsley said.

A similar evolutionary paradox can be seen with sickle cell anaemia, a condition in which a low number of red blood cells makes it difficult to carry adequate oxygen throughout the body, Kingsley said. A genetic variant causes a high rate of the disease in African populations. But that variant was favoured because it also confers protection against malaria.

“The genome is complex and our evolutionary history is complex,” said Terence D Capellini, one of the lead authors on the study and an associate professor in the department of human evolutionary biology at Harvard University. “Because of that complexity, relationships emerge between different aspects of our biology that may seem paradoxical. As we reveal this history of our genome and how it affects our biology, we begin to understand the connections.”

As with many aspects of evolutionary research, it’s easier to figure out what traits were favoured than it is to explain why. While shorter stature may have been a protection against the cold and icy terrain, it’s hard to be certain, said George Perry, associate professor of anthropology and biology at Pennsylvania State University, who is not affiliated with the study.

“We’re not going to know that without some combination of a time machine and an experiment we can’t do,” he said.

But detailed studies like this can help further our understanding of complex evolutionary processes and the potential consequences for modern medicine and human health, Perry said.

© 2017 The New York Times