While humans commonly suffer from chronic joint disease, chimps and gorillas almost never do. In a study published today in Nature, an international team of researchers led by scientists from the Weizmann Institute (Israel) and the University of Kyoto in collaboration with the laboratory of UPF ICREA research professor Tomàs Marquès Bonet at the Institute of Evolutionary Biology (IBE, CSIC - UPF) reveals that painful joints may be the hidden price we pay for traits that make us human. By studying hybrid human-chimpanzee cells and advanced genomic techniques they revealed that human joints underwent a dramatic evolutionary shift that made our joints more elastic but more prone to skeletal diseases. 

At first glance, it seems difficult to understand why human selection has favoured a condition that makes humans so much more prone to wear-and-tear of the joints and spine than other great apes. In comparison to chimpanzees, humans are more susceptible to conditions such as osteoarthritis, a major cause of disability and reduced quality of life, which affects hundreds of millions worldwide.

“Unlike the joints of other great apes, whose composition hasn’t changed for millions of years, human joints underwent a dramatic evolutionary shift”, says David Gokhman of the Weizmann Institute of Science, co-leader of the study. “That shift made our joints less effective at absorbing shocks and exposed us to skeletal diseases – including osteoarthritis, degeneration of the spinal discs and herniated discs – that are uncommon in other great apes, including those that reach old age”, adds Fumitaka Inoue of Kyoto University, who also co-led the research.

“A change in the in joints alongside slender bones and long legs may have favoured human evolution towards an upright position”, discloses Tomàs Marquès-Bonet, principal investigator at the IBE (CSIC-UPF) and ICREA research professor at Pompeu Fabra University. “Now we know the genetic details behind one of the most particular traits that makes us human”, he expounds.

The missing shock absorbers

To conduct a profound genetic analysis, the team made the first comprehensive atlas of the genomic regulatory features that distinguish the human skeleton from those of our closest living relatives. The atlas revealed one prominent difference. In humans cartilage is less dense because an entire group of genes responsible for producing glycosaminoglycans (GAGs) is less active than in other great apes.

“These long, brush-shaped sugar molecules make cartilage springy”, Gokhman asserts. “The atlas revealed human cartilage samples have only about one-third of GAG material compared to chimpanzees, gorillas, orangutans and bonobos”, Marquès-Bonet adds. Without abundant GAGs, cartilage is thinner, less elastic and less able to cushion the forces generated by everyday movement. Bones begin rubbing against one another, setting the stage for osteoarthritis.

“The GAG molecules themselves haven’t really changed during human evolution; what has changed is how many of them we produce”, explains Nadav Mishol, first author of the study. “Having a much larger GAG volume explains why other great apes tend not to develop osteoarthritis or other joint disorders, showing almost no signs of skeletal disease even as they age, unless their cartilage is severely damaged by trauma”.

“Humans, in comparison, start life with much less cartilage, meaning that we are less effective at cushioning the joints”, Inoue points out. “Since cartilage has almost no capacity to regenerate, decades of use gradually erode this already limited reserve, making joint disease much more likely later in life”.

“The decreased production of GAGs is the most extreme genetic change our skeleton has undergone in the course of evolution”, Gokhman says. “We believe we've found an evolutionary basis for the reason humans are so susceptible to osteoarthritis”.

Why evolution favoured weaker joints

The in-depth genetic analysis of this study could open new avenues for studying osteoarthritis, as it identifies the genetic mechanisms behind cartilage thinning. This could help to identify people at risk, leading to prevention and perhaps even improved therapies.

“Someone may ask whether evolution has preserved a feature –having thinner cartilage– that is problematic”, Gokhman explains. “Often, evolution favours traits that improve reproductive success, even if they carry costs later in life”, the scientist adds. Whether controversial or not, it is clear that this is a trait that distinguishes humans from other great apes.

About the study

This study is the result of a collaboration also involving Katharina Lange, Gal Bodek, Dr. Aya Kigel, Noam Priel, Nachshon Egyes, Omer Ronen, Itamar Nini, Dr. Amit Philosoph, Adi Rozenblatt, Guy Hirsh, Yael Elboim, Sergey Viukov, Idan Korenfeld, prof. Jacob H. Hanna and Dr. Simon Fishilevich of Weizmann’s Molecular Genetics Department; Dr. Zicong Zhang and Dr. Rika Tsujikawa of Kyoto University; Dr. Liat Rotenstreich and Dr. Assaf Marom of the Technion – Israel Institute of Technology; Sira Martinez of the European Molecular Biology Laboratory, Barcelona, Spain; Dr. Silvia Beltramone, Dr. Lucas Esteban Wange, María Torralvo of the Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain; Mythili Damal Kandadai, Océane Cluzeau and prof. Evie Vereecke of KU Leuven; Dr. Malka Nissim-Rafinia and prof. Eran Meshorer of the Hebrew University of Jerusalem; prof. Martin Kuhlwilm of the University of Vienna; and prof. Guillaume Bourque of McGill University.