Muscle gene linked to human brain expansion

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 didnít 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 doesnít 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 ancestorsí 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 mammalsí 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.

Did You Know?

  • Not only are chimpanzees our closest relatives, but we are also theirs: humans are genetically closer to chimpanzees than gorillas are (Source: D.E. Wildman et al., Proc Natl Acad Sci U S A, 2003).
  • Most monkeys have tails, while great apes -- chimpanzees, bonobo chimpanzees, gorillas, and orangutans -- do not (Source: Smithsonian National Zoological Park).
  • The last common ancestor of humans and chimpanzees lived between 5 and 6 million years ago (Source: D.E. Wildman et al., Proc Natl Acad Sci U S A, 2003).
  • The first primate began to evolve about 85 million years ago, but primates didn't get the chance to flourish until a large asteroid hit Earth in what is now Mexico, about 65 million years ago. The impact is thought to have killed all animals over 25 kilograms, including all dinosaurs (Source: J.J. Oró, Neurosurgery, 2004).

For references and more information, see:
  1. Stedman HH, Kozyak BW, Nelson A, Thesier DM, Su LT, Low DW, Bridges CR, Shrager JB, Minugh-Purvis N, and Mitchell MA. "Myosin gene mutation correlates with anatomical changes in the human lineage," Nature, 428:415-418, 2004.PubMed
  2. Currie P. "Human genetics: muscling in on hominid evolution," Nature, 428:373-374, 2004. PubMed
  3. Pennisi E. "Human evolution. The primate bite: brawn versus brain?" Science, 303:1957, 2004. PubMed
  4. Chou HH, Hayakawa T, Diaz S, Krings M, Indriati E, Leakey M, Paabo S, Satta Y, Takahata N, and Varki A. "Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution," Proc Natl Acad Sci U S A, 99:11736-11741, 2002. PubMed
  5. Wildman, DE, Uddin, M, Liu, G, Grossman, LI, and Goodman, M. "Implications of natural selection in shaping 99.4% nonsynonymous DNA identity between humans and chimpanzees: Enlarging genus Homo, Proc Natl Acad Sci U S A, 100:7818-7188, 2003. PubMed
  6. Oró, JJ. "Evolution of the Brain: From behavior to consciousness in 3.4 billion years," Neurosurgery, 54:1287-1297, 2004. PubMed
  7. Human evolutionary tree
  8. Comparative Mammalian Brain Collections: Primates

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