By Melissa Lee Phillips Neuroscience for Kids Consultant September 2, 2004 While examining human muscle genes, a group of scientists found that a gene that didn’t work was the most interesting of all. This gene, which makes a muscle protein called myosin, has a mutation in its DNA sequence. The myosin protein it produces is much shorter in humans than it is in our primate relatives. Also, the human version doesn’t work correctly. The scientists think that the inactivation of this protein might have led in part to the impressively large human brain. Hansell H. Stedman and his colleagues at the University of Pennsylvania looked at DNA samples from people all over the world. All humans have the same mutated myosin gene and the same inactive form of the myosin protein. All other primates tested, including wooley monkeys, pigtail macaques, rhesus monkeys, orangutans, gorillas, bonobo chimpanzees and regular chimpanzees, have full-length versions that make active myosin proteins. This particular myosin, which the researchers named MYH16, is important in muscles of the head, especially the jaw. The researchers suspected that this defective jaw muscle gene might be related to our jaw size, because humans have much smaller jaw muscles than other primates. The average monkey or ape can bite and chew with more force than we can. Muscles are attached to bones, so changes in muscles can affect bone structure. Jaw muscles are attached to the skull. Therefore, jaw muscle strength affects the shape of the skull. Many scientists think that strong jaw muscles pull down and forward on the back of the skull. Stedman and his colleagues wondered if the weakening jaw muscle mutation they discovered could have allowed the skull bones of human ancestors to expand upward and backward. Their hypothesis was supported when they found out when the myosin mutation occurred. Using a genetic technique called molecular clock analysis, they found that the mutation in MYH16 occurred about 2.4 million years ago, in a primate species that was the ancestor of the human species (but that is extinct today). This date correlated with an important time in the fossil record. The first human-like fossil with a small jaw appears between 1.8 and 2 million years ago, and shortly after this, the first fossils with very large skulls appear. The authors put this evidence together to speculate that the myosin mutation they discovered could have been a very important event in human evolution. Perhaps, they theorized, the weakened jaw muscles that resulted from the myosin mutation allowed our ancestors’ skull bones to expand. And perhaps these expanded skull bones allowed room for the brain to grow. They published their results in March 2004 in the journal Nature. The human brain is significantly larger than the brains of monkeys and apes. Our brains are much larger than those of chimpanzees, our closest relatives. Most scientists think that the enlargement of the human brain -- especially of the neocortex -- was a key step in the development of the technology, culture, and language that characterize us as a species. The expansion of the brain was indeed a key step in human evolution, agrees Scott W. Simpson, a paleoanthropologist at Case Western Reserve University in Cleveland, Ohio. But allowing a skull to become bigger does not necessarily mean the brain inside it will expand, he points out. There must be some genetic instructions telling the brain to become bigger, Simpson says, and these genetic changes would be unrelated to this jaw muscle mutation. "In principle, anything is possible when it comes to human evolution, since it only happened once," says Ajit P. Varki, a professor of medicine at the University of California in San Diego. "In practice, it is likely that many factors are involved in something like brain expansion." Also, Varki adds, many things happened at about the time that the first larger-brained human ancestors appeared in the fossil record. His lab has also found a gene mutation that occurred at about the same time in human evolution. Because of that mutation, an acid that is present at low levels in other mammals’ brains is completely missing from the human brain. "We have also speculated about its possible role in brain changes," Varki says. Not all genetic differences between humans and other primates were significant in human evolution, Simpson cautions. "There are undoubtedly other gene sequences that distinguish us from apes, yet have no function," he says. "With the chimp genome near completion, is it increasingly clear that the answers about 'human uniqueness' are not going to come easy," says Varki.