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Thursday, Feb. 7, 2002
By ROWAN HOOPER
Humans have practiced selective breeding for thousands of years to develop plants, animals and fungi better suited for human use than they are in their natural states. No genetic engineering is required, yet the genes of selected strains are different, "improved." Even people opposed to genetic modification would presumably agree that "ordinary" selection, domestication and farming methods are acceptable -- indeed, where would we be without them? To paraphrase Falstaff, banish plump Jack (and the strain of yeast that makes his beer), and you banish all the world.
The father of modern agriculture would have to be Luther Burbank (1849-1926), who devoted his life to plant breeding, developing more than 800 strains of different vegetables, fruit and flowers. His hybridization and selection experiments in Massachusetts and California were conducted on a huge scale, involving millions of plants. He developed the Burbank potato, used in Ireland to help combat the blight, 113 varieties of plums and 50 different lilies. His experiments had a worldwide influence on farming.
Now scientists at Maxygen in California and Eli Lilly and Co. in Indianapolis have developed a technique -- DNA shuffling -- that could have as profound an influence on biotechnology and modern food production as Burbank had on agriculture. DNA shuffling allows breeding and selection to be carried out at far faster rates than are currently possible, yet the technique relies entirely on natural evolutionary methods.
The researchers, led by Ying-Xin Zhang, publish their results in today's Nature.
Evolution occurs when genes vary, and when the organisms they produce differ in their survival ability. In classical breeding, two parent individuals are crossed (or mated) and the breeder selects among their offspring those that are the best at whatever the breeder is interested in, say, yeast that is better at converting sugar to alcohol. Offspring can sometimes do things better than their parents because of recombination, the process whereby new versions of genes are made by the mixing up of the parents' genetic material.
But conventional breeding methods, though powerful, are limited because they use DNA from only one set of parents. The new technique of DNA shuffling uses DNA fragments (instead of entire genomes) and so can create individuals with DNA from two or more sets of parents. Zhang and colleagues refer to their technique, deriving DNA from multiple parents, as "hypersexual." It's analogous to condensing the useful information from a library of books into a single volume.
The researchers tried their technique on a bacteria, Streptomyces, which produces tylosin, an industrially important antibiotic. Animals have sex to make offspring, but bacterial sex is about the exchange of DNA between two bacteria. When a bacterium wants to create offspring, sex is not necessary: It simply splits in two.
"Genome shuffling provides a means to cross many parents with each other, as opposed to crossing only two," Stephen del Cardayre, a co-author of the Nature paper, said in an e-mail interview.
After two rounds of genome shuffling, the new Streptomyces strain produced nine times the amount of tylosin as did the original strain. To get the same increase in production by conventional breeding techniques would have taken far longer.
"Tylosin is an antibiotic used in animal health and nutrition," said del Cardayre. "Our findings for tylosin are applicable to many other products and therapeutic areas."
The researchers suggest that similar shuffling processes could be used on higher organisms, too. And because the technique relies on natural recombination, they escape the wrath of the GM lobby.
"To our knowledge, our technique is not considered genetic modification, just as plant breeding is not considered genetic modification," said del Cardayre. "In some ways we are doing what farmers, breeders, bakers and brewers have been doing for thousands of years, and microbiologists have been doing for about 100 years: developing useful organisms to produce products to assist human civilization."
"Luther Burbank produced, through breeding, new organisms of extreme utility to society," said del Cardayre. "These organisms, of course, would not have likely evolved on their own without the selective environment of man. Yes, we are hoping to carry out similar achievements -- but on a much more accelerated time scale."
E-mail Rowan Hooper at firstname.lastname@example.org