Science in Society Archive

Rice is Life series: 1

Public/Private Partnerships Too Close for Comfort?

Is the relationship between public and private getting too cosy for comfort in the rice genome sequencing efforts? Dr. Mae-Wan Ho asks.

Two groups have simultaneously published rough drafts of the rice genome: Yang Huanming and colleagues at the Beijing Genomics Institute (BGI) on the indica subspecies, the most widely cultivated in China and most of the rest of Asia, and Stephen Goff's team of the Switzerland-based biotech giant Syngenta on the japonica subspecies, grown in Japan and other countries with temperate climates. Just as the publication of the human genome sequence last year was hailed as the "beginning of a new era of biology". The rice genome is expected to transform agricultural sciences similarly.

The publication was marked by controversy over the conditions Science is publishing the draft from Syngenta without requiring full disclosure of the sequence (see "Has Science compromised science?" this series), as in the case of the human genome sequence. Despite that, there has been much more co-operation between the public and the private groups. The new cosy relationship may suit the scientists involved, but it is not clear how it will affect the rest of society so long as the threat of corporate ownership through gene patenting remains (see CGIAR - science for the poor or procurer for the rich?) The role of the BGI is crucial. China has come up from behind to get its own rough draft of the rice genome (see "Breaching the knowledge monopoly", this issue) and promptly deposited the data on the public database, in line with Yang's insistence that knowledge must be made accessible to all. But Syngenta is already trying to engineer a merger of all the public and private groups on grounds that it would accelerate the completion.

The International Rice Genome Sequencing Project (IRGSP), a consortium of publicly funded laboratories somewhat similar to the Human Genome Project, led by Japan, have been working on japonica for nearly 5 years. The projected completion date was 2008. Two years ago, however, the US-based Monsanto announced it had completed a rough draft of the japonica genome in conjunction with the University of Washington, Seattle. The company promised to share the data with individual researchers of the IRGSP.

The approach to sequencing taken by both the IRGSP and Monsanto has been rather conventional. This involved mapping the genome first, then sequencing clones located to different chromosomes and piecing them together into contiguous sequences (contigs). Both BGI and Syngenta have opted for the newer whole-genome shotgun approach that enabled them, especially BGI, to complete the rough drafts at "lightning speed". BGI announced its plan to sequence the indica subspecies in May 2000, and had the rough draft by October 2001! In the shot-gun approach, the entire genome is broken up into pieces and sequenced. Then through the brute strength of powerful supercomputers and a software program, the sequences are assembled into contigs through ends that overlap. Of course, the fact that a large number of sequences are already mapped and deposited in the public database GenBank means that the task is made much easier.

This shot-gun approach was taken by maverick Craig Venter in sequencing the human genome, enabling his private company Celera to beat the public consortium, much to the latter's consternation, and to this day, Venter has been condemned and criticised.

The IRGSP is now worried that funding may dry up before the numerous gaps are filled and errors corrected, which they estimate would take another three years.

Why this interest in the rice genome? Was it because of its importance to the Third World? Actually, it was precisely of its importance to the third world that there has been so little interest in it. Researchers in China and Japan, independently, have begun studying the rice genome almost 20 years ago when no commercial company and few European and American laboratories had any interest. That changed in the early 1990s, when it dawned on researchers that rice is "the Rosetta stone" of cereals, says Chris Somerville, molecular biologist from Stanford University. Rice has the smallest genome size of common cereals, and tend to have the same genes in the same order. So, knowing the rice genome sequence can enable researchers to decipher the much bigger genomes of cereals that are important for rich countries.

Somerville claims no one makes money on rice seeds, and companies are interested because of the potential payoff in the markets for maize, barley, sorghum and wheat seeds. He is wrong. The US is growing and exporting rice, and companies like Monsanto are aggressively targeting the Third World markets for all cereals.

The idea of an international consortium to sequence rice arose from informal discussions in early 1997. That September, Rockefeller foundation supported a small strategy meeting at which a group of molecular biologists decided on sequencing japonica because Japan had already started on it since 1991. Five months later, the first IRGSP meeting was held in Tsukuba, Japan. Representatives from Japan, US, UK, South Korea and China drew up guidelines and divided up the 12 chromosomes in the rice genome for sequencing.

Start-up funds were provided to the US lab by Rockefeller Foundation and Syngenta, and the laboratory only won government support in 1999. But no government funding was forthcoming for any other group except for Japan. France, Taiwan and Brazil joined in later to help out.

The first blow to the IRGSP came in April 2000, when Monsanto announced it had sequenced the japonica genome in conjunction with the University of Washington and the Institute for Systems Biology in Seattle. Although very incomplete, the sequence was very informative, and Monsanto promised to share the sequence information with academic researchers and with the IRGSP, which it did. This boosted the efforts of the IRGSP, but not enough.

By January 2001, Syngenta reported it, too, had sequenced japonica. It had contracted Myriad Genetics in Salt Lake City, Utah, to sequence rice and other cereals for $30 million.

The real surprise was the BGI, which, from start to finish, took just 18 months to do the job. Yang says that with most of the other efforts focused on japonica, "there was a feeling that China should sequence its own rice."

Whereas the Beijing group has made all its data public, depositing them in GenBank, Syngenta is making its sequence available on a rather restricted basis only through its own website and on a CD-ROM. In the meantime, the company's researchers are collaborating with interested researchers, about 65 labs in 11 countries have made use of the information. This compares poorly with the 350 researchers who have used the BGI data since it was deposited in GenBank.

The IRGSP is now under pressure to finish its work, and has said it will produce its own draft by December 2002. It has already placed the data for over 230Mb in the public database, and three chromosomes are nearly finished.

The major worry is how it will affect the poor, for whom rice is literally life itself?

What's the rice genome like?

  • The indica genome has 466 million basepairs (Mb), only 430 of which are in the active functional (euchromatic) regions.
  • It is estimated to contain 46 022 to 55 615 genes according to the BGI for the indica genome and 32 000 to 50 000 genes according to Syngenta for japonica, many more than the 30 000 to 40 000 genes in the human genome
  • Repetitive DNA accounts for 42 to 45% of the rice genome. The most abundant repeats are miniature inverted-repeat transposable elements (MITES), there are 98 000 or more copies, which constitutes about 4% of the rice genome.
  • Retrotransposons (jumping genes that use reverse transcription) are the most numerous large repeats, they account for more than 15% of the rice genome.
  • More than 80% of the genes of Arabidopsis thaliana - the smallest dicotyledon plant and the first plant to have its genome sequenced - have counterparts in the rice genome. (Rice is a monocot, the other major division of flowering plants that include all grasses.)
  • Genes homologous to 98% of the known maize and wheat genes have been identified in the rice genome.
  • Only 49.4% of predicted rice genes had a homologue in A. thaliana, in other words, over half of the rice genes are previously unknown.
  • Unlike human genes where alternative splicing produce many proteins from the same genes, rice gets its protein diversity simply by having more genes than human.

Article first published 19/04/02


Sources:

  1. "Rice: boiled down to bare essentials" by Dennis Normile and Elizabeth Pennisi, Science 2002, 296, 32-6.
  2. "Rice genome sequencers cook up merger2 Declan Butler, Nature 2002, 416, 573.
  3. Yu J, et al. A draft sequence of the rice genome (Oryza sativa L. ssp. indica). Science 2002, 296, 79-92.
  4. Goff SA. Et al. A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 2002, 296, 92-100.

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