This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Human and chimpanzee genomes are more than 98% identical, and the genes themselves barely differ. The changes that make us human are thought to hide instead in the DNA that controls when and where genes switch on.
A team led by Associate Professor Fumitaka Inoue and researcher Yizhi Yan at Kyoto University's Institute for the Advanced Study of Human Biology (WPI-ASHBi), together with Principal Investigator David Gokhman and Nadav Mishol at the Weizmann Institute of Science, has now built the world's first functional atlas of the human-specific gene-control changes behind our skeleton. Combining two powerful techniques (massively parallel reporter assays, or MPRA, and human-ape hybrid cells), they discovered that a family of molecules called glycosaminoglycans (GAGs), which cushion and maintain our cartilage, has been dialed down over the course of human evolution. The finding offers a new window onto how the human skeleton took its shape, and onto why we are so uniquely susceptible to skeletal disease.
The work has been published in Nature. Compared with other great apes, humans possess a suite of remarkable traits: large brains and advanced cognition, complex speech and a skeleton built for upright, two-legged walking. Understanding how these features arose is not merely a question of natural history: It is central to understanding, and ultimately treating, diseases that are disproportionately common in humans.
But while these traits are well described at the level of the body, the specific DNA changes that helped produce them have remained largely unknown. Pinpointing which genetic differences matter, and how they act, has long been one of the central challenges in studying human evolution. The human genome contains roughly 3 billion DNA "letters" and differs from the chimpanzee genome by only about 1% to 4%, depending on how those differences are counted.
The protein-coding regions are almost identical between the two species. This has led scientists to conclude that much of what drives human evolution lies outside these regions, in noncoding regulatory sequences that determine when, where and how strongly genes are turned on. The challenge has been technical: For any given sequence, it has been extremely difficult to determine whether a human-specific change actually alters gene activity or is simply a harmless bystander.
In this study, the researchers set out to overcome this bottleneck by focusing on the human skeleton. They combined two complementary experimental approaches to identify, on a genomewide scale, the regulatory changes that shaped skeletal evolution. First, the team compared the genomes of more than 15,000 people with those of 139 great apes, including chimpanzees, bonobos, gorillas and orangutans, and identified roughly 5.7 million changes that arose only along the human lineage.
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