"Genome Shuffling" May Speed Production of Antibiotics

Bijal P. Trivedi
National Geographic Today
February 8, 2002

The "genome shuffle" sounds like the latest dance hall craze. In fact, it's a new method to accelerate evolution.

Researchers at a Californian biotech company have used the technique to produce a rapidly evolved strain of bacteria that can crank out up to eight times more antibiotics than its "parents."

Conventional breeding is generally used to improve plant and animal stocks, but the process is slow and the quality of the offspring cannot be guaranteed.

Now, scientists at Maxygen in Redwood City, California, have developed a method to "breed" an entire population of bacteria with all other members of that population and then choose the best offspring.

Stephen del Cardayré and his colleagues took ten mutants of the bacteria Streptomyces fradiae—which were all slightly better than the non-mutated parents at producing the antibiotic tylosin—and removed the tough outer layer, called the cell wall.

Without a cell wall, the bacterium's complete set of DNA—its genome—and all the other biological machinery that enables it to function are held together in a microscopic fatty sac.

These fatty sacs can merge, producing a large fatty sac with two bacterial genomes. Within this larger fat sac the two genomes mingle, exchange pieces, and eventually form two bacteria, each with its own hybrid genome.

Like Card Shuffling

The process is rather like shuffling and splitting two decks of cards. If you shuffle together a red deck and a green deck of cards (the parent decks) and then split it, there will be two decks, each with a combination of red and green cards (the hybrid offspring).

If the process is repeated and the hybrids are shuffled with other hydrid decks—a yellow deck and a blue deck, for example—and then split, the offspring of this second shuffle will have four colors: red, green, blue, and yellow.

"This is exactly what happens in nature, but we are helping the bacteria overcome their geographical boundaries and combine their genetic material," said del Cardayré.

When shuffling is repeated several times—combining hybrids with hybrids—the result is a collection of bacteria, each of which has many parents.

The next step is to test these shuffled hybrid bacteria for a desired characteristic—in this case, the ability to produce large quantities of an antibiotic.

Continued on Next Page >>




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