Genetic code once written off as meaningless played a potential role in the evolution of the human ability to hold tools and walk upright

The study is the latest in a long line of evidence to show that the genetics textbooks will have to be rewritten. It underlines how, even though the human genetic code was read letter by letter for the first time in 2000, geneticists are still struggling to figure out what it means almost a decade later. When scientists refer to genes, they mean stretches of DNA code that contain the instructions to make the proteins that build and operate the body. When the genome was first unveiled, it was thought all human genes resided in only around 1.5 per cent of the cell's DNA, prompting some scientists so dismiss the other 98.5 per cent as "junk". Now, in the journal Science, Dr James Noonan of Yale University and colleagues report that one of these supposed non coding "junk" regions may have played a starring role in the evolutionary changes in human limbs that enabled us to manipulate tools and to walk upright. The comparison of the human, chimpanzee, rhesus macaque and other genetic codes provided evidence that changes in junk areas of the genome helped to separate us from our ape ancestors, notably by "humanising" our hands and feet. Working with the Lawrence Berkeley National Laboratory in California, the Genome Institute of Singapore, and the Medical Research Council's Human Genetics Unit in Edinburgh, Dr Noonan searched vast regions of the human genome for DNA sequences whose function may have changed during the evolution of humans from our ape-like ancestors. The most rapidly evolving sequence they identified, termed HACNS1, is highly conserved among vertebrate species - that is, it hardly varies - but has accumulated variations in 16 letters since the divergence of humans and chimpanzees from a common ancestor six million years ago. This was especially surprising, as the human and chimpanzee genomes are extremely similar overall, Dr Noonan said. The importance of the changes in HACNS1 was confirmed bystudies that showed the same stretch of code could turn on a "reporter gene" in developing mouse limbs, in contrast to the equivalent chimpanzee and rhesus sequences. Most intriguing for human evolution, the human sequence influenced the use of genes at the base of the primordial thumb in the forelimb and the great toe in the hind limb. The results provided tantalizing, but researchers say preliminary, evidence that the functional changes in HACNS1 may have contributed to adaptations in the human ankle, foot, thumb and wrist-- critical advantages that underlie the evolutionary success of our species. Remarkably, some five per cent of the genome - including DNA in addition to that found in genes - is similar in a range of mammals, from dog to human, suggesting it plays a crucial enough role for evolution to preserve it while species have evolved. In the last several years, scientists have also discovered that non-coding regions of the genome contain thousands of regulatory elements that act as genetic "switches" to turn genes on or off. An exhaustive analysis of one per cent of the genome, some 30 million letters of DNA, published by an international team called the ENCyclopedia of DNA Elements (Encode) Consortium, along with 28 companion papers published in the journal Genome Research, revealed that much of the "junk" DNA seems to be the cell's "operating system" that runs genes.