A new genetic atlas is helping scientists trace the DNA changes that transformed a shared primate ancestor into modern humans.
For the first time, researchers can systematically test which genetic differences between humans and chimpanzees affect gene activity.
The study, published in Nature , grew out of a collaboration among researchers at McGill University, Kyoto University and the Weizmann Institute of Science.
"Human and chimpanzee genomes are more than 98 per cent identical, but until now we had no way to know which genetic differences had meaningful biological effects," said first author Yizhi Yan, a PhD student in the Kyoto-McGill International Collaborative Program in Genomic Medicine.
Understanding those changes could reveal not only how humans evolved, but also why some diseases arise in the first place.
Insights into skeletal development and disease
As a first test of the atlas, researchers examined the effect of hundreds of thousands of DNA differences on gene expression in skeletal cells.
"We were surprised to find that thousands of genetic changes appeared to have meaningful effects. That opens up a wealth of new avenues for future research," said co-author Guillaume Bourque , Professor in McGill's Department of Human Genetics and Distinguished Visiting Professor at Kyoto University.
Researchers then narrowed the field to genes linked to cartilage development.
Their analysis suggests humans evolved to have lower levels of molecules that help cartilage retain water and withstand pressure than do other great apes.
While this shift may have helped shape distinctive features of the human skeleton, it may also help explain why humans are particularly vulnerable to some skeletal disorders.
Evolutionary trade-off
The finding points to an evolutionary trade-off, the authors note.
"The genetic changes that gave humans new traits may also have created new vulnerabilities. Understanding those trade-offs can help us understand why some diseases exist today," said Bourque.
In the case of the skeleton, that could mean a better understanding of conditions affecting cartilage and bone, including osteoarthritis and osteoporosis, he added.
The team is now looking to apply the same approach to cells from other parts of the body, notably the brain, where the atlas could shed new light on the evolution of human cognition.
About the study
" The gene-regulatory evolution of the human skeleton " by Yizhi Yan, Guillaume Bourque, Fumitaka Inoue and David Gokhman et al., was published in Nature. Funding for the study was provided by research agencies and foundations in Europe, Israel, Japan and Canada, including the European Research Council, Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Israel Science Foundation and the Leakey Foundation.
