Mutation Cited in Evolution

By JOHN NOBLE WILFORD

Published: March 24, 2004

At a pivotal time in human evolution, around 2.4 million years ago, a muscle gene underwent a disabling alteration. And scientists say this could have made all the difference, leading to the enlarged brains of the lineage that evolved into modern humans.

Researchers who made the discovery said this might be the first recognized functional genetic difference between humans and the apes that can be correlated with anatomical change in the fossil record. As they said, the gene mutation may represent the beginning of the ancestral triumph of brain over brawn.

At the least, scientists said, the small mutated gene probably accounts for the more graceful human jaw, in contrast to the protruding ape jaw and facial ridges.

The discovery was made by scientists at the University of Pennsylvania School of Medicine and will be published Thursday in the journal Nature. They also described the findings in interviews last week.

"We're not suggesting that that mutation alone buys you Homo sapiens," said Dr. Hansell H. Stedman, leader of the research team. "But it lifted a constraint that leads to brain growth."

Evolutionary scientists and paleoanthropologists not involved in the project said the interpretation of the findings was intriguing and provocative. A "seductive hypothesis," one of them said, while others cautioned that the explanation probably oversimplified the causes behind the significant brain expansion that marked the emergence of the Homo lineage out of the more apelike Australopithecus species.

Even so, the findings were expected to encourage other scientists to investigate a whole range of other genes that have decisive roles in making us distinctively human. This could enable molecular biologists to establish the chronology of important steps in human evolution with greater precision.

The Penn scientists were searching for remaining genes that govern myosin, a protein that makes up muscle tissue, when they came across a piece of the human genome sequence that had been overlooked. The gene, MYH16, had apparently gone unrecognized because of a small mutation that had rendered it inactive for producing some jaw muscles for chewing and biting.

The scientists found that this myosin gene is still intact in other primates today, such as chimpanzees and macaques. They have correspondingly strong jaw muscles. An analysis of DNA samples showed the gene-inactivating mutation to be present in all modern humans worldwide. The analysis further traced the mutation's occurrence to between 2.1 million and 2.7 million years ago, probably 2.4 million.

That happened to be just prior to the appearance of major evolutionary changes in hominid fossils, the research team noted in the journal article. Some hominids with protruding jaws and small brain were soon to evolve into the first species of the genus Homo, with significantly smaller jaws, larger brains and a modern human body size. After two million years, Homo erectus was able to strike out for lands far beyond Africa.

"The mutation very possibly initiated an evolutionary cascade," said Dr. Nancy Minugh-Purvis, a paleoanthropologist involved in the project.

Dr. Stedman's group concluded that the findings "raise the intriguing possibility that the decrement in masticatory muscle size removed an evolutionary constraint on encephalization." In short, as the strong, stoutly buttressed jaw muscles declined, this allowed the skull to develop a new shape and structure, giving the brain room to grow.

In an accompanying critique, Dr. Pete Currie, a developmental biologist in Sydney, Australia, who called the hypothesis seductive, wrote that the Penn researchers presented "convincing arguments as to how the mutation could have been responsible" for the acquisition of more humanlike traits by ancestral hominids.

"I'm amazed at what they came up with," said Dr. John Fleagle, a paleoanthropologist at the State University of New York, Stony Brook. "But I'd be surprised if the interpretation is that simple."

Dr. Alan Walker, an anatomist who specializes in human evolution at Pennsylvania State University, said, "The mutation is a very interesting finding, but what it means is a different matter."

Dr. Walker and others questioned the idea that jaw muscles of the more apelike hominids were a major factor in constraining brain size. "An extremely unlikely proposition," he said.

Dr. Stedman said the cause of the mutation was unknown and probably unknowable: damage from cosmic rays perhaps, ingested toxins or other environmental exposures. Other contemporary hominid species could have been exposed to the same conditions, but for some reason, escaped with their myosin gene unaltered — and their jaws as formidable as ever. These robust but small-brain species continued to live in Africa until their line became extinct about one million years ago.

Dr. Minugh-Purvis said it was unclear how the mutation could have become fixed in the species, considering its potentially deleterious effects on survival. Perhaps other agents of change were already at work, like the transition to a richer protein diet of meat. The heavier jaws were required for grinding the mainstays, nuts and plants, in their diets.

Dr. Ken Weiss, a geneticist at Penn State, said the new research is one of a number of recent investigations into the roles of single genes in significant changes in human evolution. He agreed that the mutation could have led to some differences in the muscle structure of hominids, but other changes were already in progress that contributed to the traits that set the genus Homo apart from its predecessors.

Although he doubted the myosin gene will be a Rosetta stone of evolution, Dr. Philip Rightmire, a paleoanthropologist at the State University of New York, Binghamton, said it was intriguing that the timing of the mutation "is just bang on the mark for the emergence of genus Homo."

Scraps of fossils in East Africa suggest that the first Homo species evolved about 2.3 million years ago. The evidence for them becomes more prevalent a few hundred thousand years later.

Dr. Ian Tattersall, a paleoanthropologist at the American Museum of Natural History in New York City, said the gene mutation "could certainly be a link in a larger chain of cause and effect, but probably not the whole story."