By Pranali Dalvi
Human and chimpanzees are very similar genetically despite the stark differences in their outward appearances. So it must be just a very small portion of human genes that are responsible for everything from our upright posture to our ability to sing. What makes humans so unique?

On Jan. 14, Duke Professor of Biology Greg Wray spoke about his group’s work on the genetic and molecular processes that contribute to our uniquely human physiology and brains as a part of the Computational Biology and Bioinformatics Seminar Series.

“Humans are not the best model organisms since there is a limit to what you can do genetically and mentally. You can’t really make a human knockout (but sometimes, nature makes it for you),” Wray said.

Still, humans are immensely important to study for practical reasons. We have uniquely human courses of disease in part due to our physiological, cognitive, and mechanical properties. Also, we’re just intrinsically curious about our own bodies.

According to Wray, the answer to human uniqueness is our regulome, the genes, mRNAs, proteins, and metabolites that regulate which genes are turned on when.

This graph shows the two major shifts in diet (meat-rich diet and grain-based diet) that likely contributed to our divergence from chimpanzees and thus differential gene expression. Source: Greg Wray

One prevailing hypothesis is that human forerunners likely began diverging from chimps about 2 million years ago when we took on a meat-rich diet in the savannah. The ancestors of chimpanzees retreated to the rainforest to eat a diet consisting mostly of fruits. Our meat-rich diet seems to coincide with an increase in brain size. And today we metabolize fats much differently than chimpanzees.

Wray’s lab studied the effects of dietary changes on five tissue samples – the cerebral cortex and cerebellum of the brain, liver, fat, and skeletal muscle. What seems to have changed in chimps versus humans are genes related to neural functioning, development, and metabolism. For instance, 31 of 61 genes involved in insulin signaling are operated differently in chimps and humans. These differences in gene expression may also explain why humans are uniquely susceptible to diet-related illnesses like type II diabetes.

On the other hand, genes involved in the transcription, translation and replication of DNA, RNA processing and protein localization haven’t changed in chimps versus humans.

Fat cells also behave differently in humans versus chimps. Wray’s lab took adult stem cells from adipose tissue in both chimps and humans and challenged them with either more oleic acid (the main fatty acid in a meat-heavy diet) or more linoleic acid (the dominant fatty acid in a grain-based diet). The enzymes involved in fatty acid synthesis were more common in human adipose tissues. Wray believes that the increased fatty acid synthesis is probably responsible for building and fueling a larger human brain.

Another major shift in diet occurred during the agricultural revolution, which introduced omega-6 fatty acids into our diet along with pro-inflammatory compounds. Wray explains that the increase in grains from the shift in diet likely contributes to chronic pro-inflammatory diseases in humans, such as atherosclerosis.

“Understanding our metabolic history from an evolutionary context can potentially give us insight into some pretty prominent health concerns,” says Wray.