University of Michigan News Service – UM News

How gene duplication helps in adapting to changing environments

ANN ARBOR—As scientists piece together the genomes of more and more life forms—from fruit flies to humans—they’re finding ample evidence that new genes have often been created through the duplication of existing genes. Of the more than 40,000 genes in the human genome, for example, about 15,000 appear to have been produced by gene duplication. Evolutionary theories assert that some of these duplicated genes may acquire new functions and take on new roles. But exactly how do these changes occur? And do they, as scientists suspect, really help organisms adapt to their environments?

New answers to these questions come from a study of leaf-eating monkeys by researchers at the University of Michigan, the National Institutes of Health, and the Chinese Academy of Sciences. In the work, published online March 4 by Nature Genetics, U-M’s Jianzhi Zhang and colleagues show how a duplicated copy of a gene encoding a pancreatic enzyme has evolved to help the monkeys cope with an unusual diet.

The monkeys belong to a subfamily of Old World monkeys called colobines, says Zhang, an assistant professor in the Departments of Ecology and Evolutionary Biology and Molecular, Cellular and Developmental Biology. “Colobines are different from other monkeys in that they primarily eat leaves rather than fruit or insects, and leaves are very difficult to digest,” he explains. But the monkeys manage with a digestive system similar to a cow’s. Bacteria in the gut ferment the leaves and take up nutrients that are released in the process. The monkeys, in turn, digest the bacteria to recover the nutrients, such as protein and ribonucleic acid (RNA), a particularly important source of nitrogen in leaf eaters.

Zhang and colleagues were particularly interested in a pancreatic enzyme, RNASE1, which breaks down bacterial RNA. Most primates have one gene encoding the enzyme, but the researchers found that the douc langur, a colobine monkey from Asia, has two—one encodes RNASE1, and its duplicate encodes a new enzyme, which they dubbed RNASE1B. The duplication occurred about 4 million years ago, after colobines split off from the other Old World monkeys, Zhang’s analysis showed. Through a series of computations and experiments, the researchers determined that the original gene encoding RNASE1 remained unchanged after duplication, but its twin, which encodes RNASE1B, changed rapidly. Furthermore, the changes were not random; most caused the enzyme to become more negatively charged, which could affect its interaction with the RNA it degrades.

Next, Zhang’s group tested the activity of RNASE1 and RNASE1B at different levels of acidity (pH). In the small intestine, where the enzymes do their work, pH levels range from 7.4 to 8 in humans and most monkeys, but the levels are more acidic—around 6 to 7—in colobines. Interestingly, the researchers found that the original enzyme works best at pH 7.4, but the new enzyme is most effective at pH 6.3—the acidity of the colobine small intestine. In fact, RNASE1B works six times better than RNASE1 under the more acidic conditions.

“Our results suggest that this is an adaptation to the more acidic environment of the small intestine in colobine monkeys,” says Zhang. But if the new enzyme is so much more efficient, why has not natural selection done away with the old one? Apparently, it still performs an important function, Zhang speculates.

“We know that in humans, RNASE1 has two functions: to digest dietary RNA and to degrade double stranded RNA, perhaps as a defense against double-stranded RNA viruses,” says Zhang. In the douc langur, RNASE1B has become super-efficient at the first job, but has lost the ability to do the second, his research shows. RNASE1, though upstaged in the first role, still carries out the second.

“So now they have different jobs to do,” says Zhang. “Before the duplication, you have one enzyme doing two jobs. After duplication, you have two enzymes, each doing just one job, but doing it better than the other.”

Zhang’s analysis shows that the duplication occurred some six million years after colobines began eating leaves. “So leaf-eating did not depend on the new gene, but the new gene apparently improved the efficiency,” he concludes.

As for the evolutionary forces involved in adaptation to a changing environment, scientists have debated whether positive selection for a new function is more important than relaxation of the selective pressures that maintain an old function. The new research suggests that, at least in this case, both were necessary.

National Institutes of HealthEcology and Evolutionary Biology