Humans and chimpanzees share more than 99 percent of the same DNA. So why are we vastly different from our closest primate relatives?

Scientists have long suspected that what makes us human isn’t just our genes, but how we regulate them. A study from Charles Danko, assistant professor in Cornell’s College of Veterinary Medicine, supports this idea. Danko and co-author John Lis, professor in molecular biology and genetics, describe small differences between humans and chimps in regions of DNA called enhancers, which help turn on nearby genes. These changes point to specific ways that human and chimp evolution has diverged, and have the potential to play a role in inherited human diseases, according to their paper in Nature Ecology and Evolution.

They used a technique called PRO-seq to map where the RNA polymerase – the molecular copy machine that copies DNA into RNA – sits on the genome. PRO-seq gives a precise picture of the genes that a cell is using at any given time. With the help of Baker Institute of Animal Health colleague Elia Tait-Wojno, assistant professor of microbiology and immunology, the team used this technique to analyze immune cells from humans, chimpanzees and rhesus macaque monkeys.

According to the researchers, when lots of enhancers target the same gene, they undergo evolutionary changes as a unit. This helps cells protect themselves from mutations in individual enhancers and ensures that important genes are transcribed at constant levels, regardless of these mutations. The redundancy of the enhancers also frees them up to change and acquire new functions so that species can rapidly adapt to new situations.

“How the elements work together is important for understanding how they evolve,” said Danko. “This is important for establishing differences between humans and chimpanzees.”

The researchers are working to perfect this technique to allow them to analyze difficult samples, such as primary tumors. Danko also plans to investigate how enhancers interact with each other by folding DNA inside the cell.

The team collaborated with Cold Spring Harbor Laboratory to complete this research.

Patricia Waldron is a freelance writer.