September 10, 2007 New York Times

Study Finds Evidence of Genetic Response to Diet

Could people one day evolve to eat rich food while remaining perfectly slim and svelte?

This may not be so wild a fantasy. It is becoming clear that the human genome does respond to changes in diet, even though it takes many generations to do so.

Researchers studying the enzyme that converts starch to simple sugars like glucose have found that people living in countries with a high-starch diet produce considerably more of the enzyme than people who eat a low-starch diet.

The reason is an evolutionary one. People in high-starch countries have many extra copies of the amylase gene which makes the starch-converting enzyme, a group led by George H. Perry of Arizona State University and Nathaniel J. Dominy of the University of California, Santa Cruz, reported yesterday in the journal Nature Genetics.

The production of the extra copies seems to have been favored by natural selection, according to a genetic test, the authors say. If so, the selective pressure could have occurred when people first started to grow cereals like wheat and barley at the beginning of the Neolithic revolution some 10,000 years ago, or even much earlier.

Paleoanthropologists have long wondered what change in the usual primate diet of fruit and nuts enabled the emerging human lineage to support a brain that eventually swelled to three times the size of chimpanzees’.

Neural tissue requires large amounts of energy, and the usual assumption is that humans began to eat meat some 2.5 million years ago when brain volume started to expand. But another possibility is that the extra nutrients came from starch.

As soon as the human lineage split from the chimp’s about five million years ago and started to live in open woodland, its diet may have expanded to include tubers, corms and the other underground structures in which plants store starch. In support of this idea, Dr. Dominy, a paleoanthropologist, said that the teeth of early humans “are not well suited for eating meat.”

Chimpanzees, whose fruit-based diet does not include much starch, have a single amylase gene. Dr. Dominy, Dr. Perry and their colleagues believe that the number of amylase genes in the human genome had started to expand by at least 200,000 years ago and perhaps much earlier, but the exact date cannot yet be determined.

Richard Wrangham, a primatologist at Harvard and an advocate of the tuber-eating thesis, said the amylase finding was a convincing insight into the different digestive physiology of people and chimps, but that the date of 200,000 years ago, derived from limited genetic information, was not old enough to give direct support to his ideas.

The amylase enzyme studied by Dr. Perry’s team exists in the saliva, where it predigests starch and lets glucose get absorbed from the mouth into bloodstream. The evolutionary advantage of this strange arrangement is not clear, but it could provide the body with energy during episodes of diarrhea, or might protect against diarrhea. Or it could just make the digestion of starch more efficient.

Whatever the exact mechanism, the extra copies of the amylase gene seem to have arisen through positive selection, the researchers said. Their conclusion is based on comparing the genomes of the Japanese and the Yakut, a Siberian people who eat mostly reindeer. Dr. Perry, a geneticist, said he could not tell whether the Japanese, who have a high-starch diet, including rice, had gained the extra copies of the gene or whether the Yakut had lost theirs.

Geneticists realized only in 2004 that having extra copies of genes was a widespread form of variation in the human genome. Many of the extra copies seem to have arisen through mistakes in the duplication process that doubles the number of chromosomes in dividing cells. The effect of these extra copies is largely unknown and the story of the amylase gene is one of the first to be understood, at least to some degree.

Dr. Perry and his team started their research by having undergraduates at Arizona State University give samples of saliva, which were analyzed for amylase. The researchers found the amount of amylase a person produced was correlated with the number of copies they possessed of the amyloid gene, which ranged from 2 to 15. The copies are arranged in the genome like a string of beads, with each gene being about 120,000 units of DNA in length.

Wondering whether the copy number varied with diet, the researchers then collected saliva and blood samples from the Yakut and other low-starch eating populations, showing that this was indeed the case.