A network apart
Genetically, we are almost the same as chimpanzees. But an important difference is how our genes form highly complex networks.
One of mans closest evolutionary relatives is the chimpanzee. The split between our species occurred about twelve million years ago. But genetically, we remain almost the same: More than 97 per cent of human genetic material is identical to the chimpanzee’s.
So why are we so different?
The answer lies not in our genes as such. It is in how our genes work and interact, including those we have in common. This difference is particularly evident in the brain, where human genes are linked more closely in networks than the same genes in monkeys. Norwegian and US scientists uncovered this difference by studying a large number of genes from both species.
How did we become human?
“How did we become human? What is the difference between us and chimpanzees?” asks Eivind Almaas, a professor of systems biology at NTNU, who participated in the genetic study conducted at the University of Illinois.
“One possibility is that a random gene, one here or one there, undergoes small mutations that create lasting change in the species. But this kind of change will probably have only small effects. Another possibility is that the selected changes in some special genes – transcription factors – trigger modified or new genetic programmes in different parts of the body. Our question was whether this last possibility may explain differences in human and chimpanzee brains,” says Almaas.
The body’s traffic lights
A gene itself has no other function than to be a working drawing for the essential building blocks in an organism’s cells. Organisms use genes like a recipe to build a molecule, usually a protein. The molecule then carries out what we commonly refer to as the gene’s function.
Different proteins are required for construction and maintenance of cells and molecules, and play important roles in all bodily functions. In the genes that are called transcription factors, however, the protein has a special function: It is sent exclusively to control other genes – which means it controls the production and function of other proteins.
Transcription factors turn other genes on and off, dampen or strengthen them, coordinate and regulate them. They can be compared to an advanced traffic lights system at a complicated and congested intersection. The researchers suspected that the difference between us and chimpanzees could be traced to coordinated changes in select transcription factors, and how they are used.
1.2 million genetic tests
The scientists took the previous results of tissue samples from five chimpanzees and six humans. Here, the gene activity in the heart, kidneys, liver, testicles and brain of both species was analysed using what are called DNA microarrays, a tool that enables a single experiment to detect the level of activity for tens of thousands of genes in cell or tissue samples.
The researchers compared the activity levels in a total of 21 000 individual genes that were identical for both species in the 55 samples. They were all measured at the mRNA stage. This is an intermediate stage where a replica of the gene is on the way out of the cell to produce a protein, and reflects the activity level of the gene.
It turned out that about every fifth gene behaved differently in humans and chimpanzees in the samples that were taken from the brain, heart, kidney and liver, while almost half of the genes behaved differently in testicular tissue. In all, the group was able to identify 90 transcription factors that were particularly different in humans and chimpanzees, says Almaas.
A dense network
What was it that these transcription factors did in the brain? Simply put: They formed networks. In all, around 1400 genes were affected. And most of these 1400 genes were influenced by more than one transcription factor.
Almaas found that the network in the chimpanzee brain was quite similar to the human network – except that the human networks were much denser and had greater interaction. In addition, the function of these genes is associated with increased energy metabolism, the transport of molecules and protein production, all needed to maintain the physically much larger human brain.
One special group of transcription factors is called KRAB-ZNF. This is the most common type of transcription factor found in mammals and fully a third of them are found only in primates. The activity of these particular transcription factors was demonstrably different in the human brain than in chimpanzee.
“On average, KRAB-ZNF genes have many more mutations than other genes, in the time since we split from chimpanzees,” said Almaas. “This suggests that they have contributed to many of the important differences between us and chimpanzees.”
In collaboration with his American colleagues, Almaas will now select three or four of the genes that played very different roles in chimpanzees and humans, and will study them in detail to find out more about their function.