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First Complete Plant Genetic Sequence Is Determined

ANDREW POLLACK / New York Times 14dec00

Scientists from the United States, Europe and Japan have determined the first complete genetic sequence of a plant, an accomplishment that should deepen understanding of plant biology and provide new ways to genetically engineer crops to increase food production and improve nutrition.

The plant, Arabidopsis thaliana, is a diminutive weed that is related to the mustard plant and is worthless as a crop. But it is quickly becoming the laboratory mouse of the plant world, studied for insights that can be applied to virtually all other plants.

Indeed, genes found in Arabidopsis, commonly called thale cress, are already being tested by companies and academic scientists to make plants flower more quickly, to keep fruits from ripening too early and to produce healthier vegetable oils.

"There's thousands of applications coming down the pipeline," said Chris Somerville, director of the department of plant biology at the Carnegie Institution, professor at Stanford University and an early organizer of the sequencing project. "Our goal and I say we're going to reach it in the next decade is to understand plants like little machines. And we're going to use it to do real engineering."

Mendel Biotechnology of Hayward, Calif., is testing a gene from Arabidopsis that makes plants resistant to frost and drought. Paradigm Genetics Inc. in Research Triangle Park, N.C., said it had already identified 100 genes in Arabidopsis that could be used to design new herbicides.

"I think it has the same importance in plant biology as knowing the human genome does in human health," said John A. Ryals, Paradigm's president.

The lowly weed might even be used to study human diseases and develop drugs. There are almost 150 genes in Arabidopsis that are the counterparts of human disease genes, said Claire Fraser, president of the Institute for Genomic Research in Rockville, Md., a major participant in the project.

The completion of the sequence was announced at news conferences yesterday in Washington, London, Brussels and Tokyo and will be published in the journal Nature today. A few more papers analyzing the genome will be in Science tomorrow.

The accomplishment comes more than 100 years after the science of genetics was born with the study of another plant the pea by Gregor Mendel. Scientists are expected to publish the full sequence of the human genome early next year; genomes completed previously include the fruit fly, the C. eleganis worm and yeast.

The Arabidopsis sequence has been made available as it has been derived, so scientists have had access to parts of the sequence for years.

The genome consists of 5 pairs of chromosomes containing about 125 million base pairs, the units of the genetic code that are represented by the letters A,C,G and T. That is considerably smaller than the human genome, which has 23 pairs of chromosomes and 3.1 billion base pairs.

Using computer analysis, scientists have identified 25,498 genes. But many are duplicates, so that there are probably fewer than 15,000 unique genes, roughly on par with the fruit fly and roundworm. Estimates of how many human genes there are range from less than 30,000 to more than 130,000.

The Arabidopsis Genome Initiative began in 1996 and has involved more than 100 scientists contributed to a paper in Nature. Major participants included the University of Pennsylvania, Stanford, California- Berkeley, the Cold Spring Harbor Laboratory, the Kazusa DNA Research Institute in Japan and two European consortiums.

National Science Foundations officials estimate the total cost at $78 million, of which $44 million came from the United States government, mainly the foundation.

Arabidopsis, which is widespread in the world, was chosen as a model because its genome is small. The plant is also small, can be grown easily in a laboratory and multiplies in about six weeks, compared with months for corn and years for trees.

"In my lab we can probably grow one million plants a year," said Elliot M. Meyerowitz, a professor of biology at the California Institute of Technology and an Arabidopsis pioneer. Yet Arabidopsis is considered as similar to other plants as mammals are to one another.

"You can basically take the gene information you find in Arabidopsis and immediately translate it into other plants," said Joseph R. Ecker, a professor at the Salk Institute for Biological Studies in La Jolla, Calif. He said scientists had already found in the weed the counterpart of the wheat gene that gave birth to the Green Revolution.

Scientists said there had been little of the friction between the public and private sectors that characterized the decoding of the human genome. The Monsanto Company determined a rough sequence of a different strain of Arabidopsis but has made public about 40,000 differences between its sequence and the public one.

But for many companies, the real emphasis is to find the function of the genes, which could provide the basis for patents. Ceres Inc., a biotechnology company in Malibu, Calif., says it has filed for patents on many thousands of Arabidopsis genes. "It's a significant proportion of the genome," said Richard Flavell, chief scientific officer. He said the company was making its information public but assuming the patents are granted people using those genes commercially would need a license.

But Dr. Somerville of the Carnegie Institution said so much information had been in the public domain it might be hard for companies to get patents.

The National Science Foundation, meanwhile, has started a 10-year project to determine the functions of all the genes and how they work together. The ultimate goal is a "virtual plant" a computer model that could, say, predict the response of the plant to different environmental conditions.

Scientists say that knowledge of the genome will permit genetic engineering that can change the entire architecture of a plant, rather than just add a single trait like pest resistance, which is done now.

Detlef Weigel at the Salk Institute put an Arabidopsis gene controlling when plants flower into aspen trees, causing the trees to flower in a few months rather than 8 to 20 years. The technique could speed up plant breeding and allow crops to be grown twice in a year on the same plot of land, he said.

But Margaret Mellon, a critic of agricultural biotechnology at the Union of Concerned Scientists in Washington, said knowledge from the genome project should be used instead to improve conventional breeding or determine ideal planting conditions. "A deeper understanding of plants could lead to some really clever and useful ways of increasing yields and getting rid of pests other than strong-arming plants by moving genes into them," she said.

Another public effort is already at work on the rice genome, which has about 430 million base pairs, a relatively small number. It is expected to serve as a further model for other grains like wheat and corn, which have genomes that are so large and full of nonfunctioning DNA that they are considered impractical to sequence. Corn has about 2.6 billion base pairs and wheat more than 16 billion, several times the size of the human genome.

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