The early primates started walking on two legs some five to seven million years ago, after the earth became a cooler and drier planet and forests began to give place to grasslands. This freed their hands for manipulating tools and there is evidence to show that brain size grew rapidly, from the chimpanzee&’s less than 400cc to about 600cc in early humans of about two million years ago and the 1,300cc of the present day.

Along with greater brain size, humans have evolved to display dramatically superior intelligence, with the capacity for language, abstraction and social integration and organisation not seen in other species. Although there are differences in the genes of humans and chimpanzees, like in the parts that control speech development or hearing, that can be linked to selection through language related behaviour, the main genetic heritage is almost the same. How, then, does the human brain grow so much more than that of the chimp is a question of great interest.

J Lomax Boyd, Stephanie L Skove, Jeremy Rouanet, Louis-Jan Pilaz, Tristan Bepler, Raluca Gordan, Gregory A Wray and Debra L Silver, at Duke University in North Carolina, report in the journal Current Biology that they have discovered bits of DNA that do not code for anything but influence the expression of genes, and whose human version promotes cell division of neurons and, hence, a larger brain. The findings may lend insight into not only what makes the human brain special but also why people get some diseases such as autism and Alzheimer&’s disease whereas chimpanzees do not, says a press release from Duke University.

The genetic heritage of creatures is the long chain molecule, the DNA, contained in the nucleus of each cell of organisms. The DNA molecule is a chain of successive instances of any one of only four kinds of chemical groups, called G, A, T and C, that appear through the chain. Within the chain, each group of three successive units, or triplets, specify either any one of the 20 amino acids that build up all known proteins, or the start or end of a list of amino acids. In this way, sequences of triplets, called genes, are able to spell out the specific proteins to be assembled and, hence, the role and function of the different kinds of cells.

But each of the groups can code for hundreds or thousands of amino acids to lead to one protein and there are many thousands of proteins. DNA also contains long stretches, often the longest of all, of non-coding sequences. Hence, although each unit in DNA is only nanometres long, the DNA molecule itself is nearly three metres long. And the whole length is folded and curled to fit inside the cell nucleus just six microns in size. The result of this folding is that all parts of DNA are not always ready to get active and “expression” or the actual action of genes depends on other factors. Some of these factors are environmental and some are triggers within DNA itself, including regulator genes found in the “non-coding” part of DNA.

These are the factors that set off gene action, either at times of stress or even to decide what kind of cell the cell is to be. The main action of the DNA is brought about by enzymes called polymerases, which enable stretches of DNA to be copied and carried out into the cell for the assembly of proteins or to initiate cell division. Polymerase action is promoted or repressed by other agents, called activators or repressors, which help or interfere with polymerase binding to the relevant part, which is called the promoter. And then there are enhancers, which are found in non-coding parts of the DNA structure, that help DNA bend in a way that brings the promoter into the right position. And then there are the silencers, which can bind to other factors to prevent expression of a gene.

That the startling differences between humans and chimpanzees, when both species have such similarity in DNA, may lie in the regulatory mechanism of genes has been suspected for some time. Although there are enhancer segments that are unique to humans, none have been identified as affecting brain growth. But different groups of scientists have studied the non-coding sequences in DNA and extensive data has been collected of the parts that are conserved through the course of evolution of mammals and where there are changes in humans since the divergence from chimpanzees.

The Duke University team made use of these data bases and by a process of data mining and imaginative analysis they isolated enhancers in the DNA of humans and chimpanzees that expressed chiefly in brain tissue and early in development. They then separated the enhancers where there was a marked difference between humans and chimps and came down to a list of just 106. Of these, six appeared to affect genes that were involved brain development and they were named Human Accelerated Regulatory Enhancers, or Hare1 to Hare6. One of these, Hare 5 was located physically close to a gene, Frizzled8, which was known to be involved in brain development and disease, and the team also found that Hare5 and Frizzled8 actually made contact in brain tissue. The team then introduced the human and chimpanzee versions of Hare5 into mouse embryos to see what effect they had on early brain development. What they found was that the human version of Hares5 actually promoted the proliferation of stem cells maturing into neurons, leading to a 12 per cent larger brain than mouse embryos that received chimpanzee Hare5. “What&’s really exciting about this was that the activity differences were detected at a critical time in brain development: when neural progenitor cells are proliferating and expanding in number, just prior to producing neurons,” said researcher Debra L Silver.

The increased volume of brain is found to be in the neocortex, the region that is involved, in humans, in language and reasoning. The team of researchers now proposes to watch these two groups of newborn mice into adulthood to discover what differences there were in fullgrown brains and behaviour of the adults. The team will also see what effect other Hare sequences may have on brain development. “What we found is a piece of the genetic basis for why we have a bigger brain,” said Professor Gregory A Wray, director of the Duke Center for Genomic and Computational Biology. “… This is probably only one piece, a little piece.”

The writer can be contacted at simplescience@gmail.com