We humans are proud of our big noggins. The average human skull, which packs some 1350 cubic centimeters (cc) of brainpower, is larger than that of any other animal, relative to body size. Now a molecular biologist suggests that a recently identified gene called ASPM might be implicated in the impressive expansion hominid brains have undergone over the last 2 million years.
The work builds on studies of a rare disease called autosomal recessive primary microcephaly (MCPH). In this inherited malady, the brain is typically just 400 cc--roughly the same size as that of the early hominid Australopithecus africanus, of which "Lucy" is the best-known specimen. A earlier report concluded that the most common cause is a mutated ASPM gene (ScienceNOW, 23 September 2002).
Jianzhi Zhang of the University of Michigan, Ann Arbor, hypothesized that ASPM might have played a key role in human brain expansion. To test this hypothesis, he looked for evidence that the gene was under "positive selection," meaning that it had provided an evolutionary advantage to hominids. Zhang compared the DNA nucleotide sequence of the human version of ASPM to that of two of our great ape cousins, the chimpanzee and the orangutan, as well to more distantly related animals such as rhesus monkeys, seals, dogs, and hamsters. A gene is considered to have undergone positive selection when it has a relatively high ratio of nucleotide changes that lead to a change in the amino acid sequence of the corresponding protein, compared to changes that make no difference. This ratio was quite high in humans but much lower in chimpanzees and orangutans, Zhang reports in the December issue of Genetics.
Experts say this is strong evidence that ASPM could have contributed to human brain expansion. But other genes were probably also involved, because hominid brain expansion took place in multiple stages over 2 million years, says Ajit Varki, a molecular biologist at the University of California, San Diego. Neuroscientist Todd Preuss of Emory University in Atlanta agrees: "Nobody should conclude that ASPM is the brain-size gene."
Moreover, some researchers say, the observation that MCPH patients can speak, and that they suffer at most from moderate retardation, indicates that the ASPM gene is not key to intelligence itself--whether or not it might have played a role in scaling up the hominid brain to modern dimensions.
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