Unfavorable Today, Some Genetic Mutations Were Likely Beneficial at One Time

A recent finding published in the journal Nature Genetics suggests that a gene associated with short stature, reduced mobility, and sore joints might have played a key role in the survival of humans during the Ice Age.

The study published indicates that as early humans migrated towards colder, northern climates, the survival of those carrying a genetic mutation increased. Specifically, the mutation reduced height by about a centimeter and increased the risk of osteoarthritis by up to 80 percent. Although these traits seem less advantageous today, they were actually beneficial to early humans migrating out of Africa during the most recent Ice Age.

Dr. David Kingsley, author of the study and a professor of developmental biology at Stanford University, noted that—in many cases—evolution is a trade-off. For example, short stature may have allowed prehistoric humans to retain heat and stave off frostbite in their extremities. It also may have reduced the risk of bone fracture when traveling over icy terrains or falling from heights. On the other hand, the same gene puts humans today at risk for arthritis, as average life expectancy now increases far beyond reproductive years.

Dr. Kingsley's study looked at a gene called GDF5, which researchers in the 1990's linked specifically bone growth and joint formation. The researchers focused on the region of DNA around GDF5, a sequence they named "GROW1," in particular. They looked at this sequence in multiple human genomes to understand how the gene’s expression is affected by the DNA sequence around it.

After analyzing the sequence of GROW1 in the "1,000 Genomes Project" database, which is a collection of DNA sequences from populations around the globe, the researchers identified a change in one nucleotide that they believed could be linked to bone growth and joint formation. They discovered this change is common in Europeans and Asians but very rare in Africans. Then, to determine if the mutation actually reduced the stature of humans, rather than just being coincidental, researchers tested the mutation in mice. They found it did indeed decrease the length of the mices' long bones, thus suggesting it might do the same in humans.

Further, Dr. Kingsley found that 50 percent of the populations in Asia and Europe have the GDF5 mutation. In fact, in some Asian populations, up to 90 percent of people have the mutation. And though the modification plays a small role in increasing an individual's arthritis risk, it can have a significant influence at the population level.

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

The same evolutionary anomaly occurs with sickle cell anemia, a disorder of the blood caused by inheritance of abnormal hemoglobin. This genetic mutation affects millions of Africans and causes a high rate of disease; however, it also protects against malaria.

“The genome is complex and our evolutionary history is complex,” said Dr. Terence D. Capellini, author on the study with Dr. Kingsley and a professor in the Department of Human Evolutionary Biology at Harvard.

Dr. Capellini researches the DNA changes underlying human and non-human primate biological adaptations. “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,” he said.

Dr. George Perry, a professor of biology at Pennsylvania State University who is not affiliated with the study, said that when researching evolutionary aspects, it’s easier to figure out what traits were favored by certain groups at specific points in time than it is to explain why. While shorter stature may have been an evolutionary mutation to try to protect against the cold and icy terrain for early people in the Ice Age, it’s hard to be certain.

Ultimately, studies like Dr. Kingsley's and Dr. Capellini's guide us towards a better understanding of complex evolutionary processes and the potential consequences for modern medicine and human health.

[Source: The New York Times]