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Organic Misconceptions and Nutritional Genomics
Graeme O'Neill Australian Life Scientist

'Dean Della Penna says we are in the midst of a golden period for research into plant metabolism.'

The comforting but questionable assumption that nature knows best strongly influences the food-buying preferences of Western consumers. The booming organic food industry takes the mindset a step further, by using only "natural" fertilisers and pesticides.

Unfortunately, hundreds of millions of people in the world's poorer nations suffer because "natural" does not mean optimal nutrition. Professor Dean DellaPenna, professor of biochemistry at Michigan State University, would like to make it so.

DellaPenna is a strong proponent of fine-tuning the metabolism of major crop species to improve both the concentration and balance of essential micronutrients like iron, the two major lipid-soluble vitamins - the vitamin A precursor, beta carotene, and vitamin E - and other minerals.

The world's No 1 human staple, rice, is naturally deficient in beta-carotene and iron. Some 400 million children in rice-eating countries suffer from poor vision and often blindness, because of vitamin A deficiency. Rice is also lacking in iron, causing anaemia and pregnancy complications in millions of women.

DellaPenna, a plenary speaker at ComBio 2008, will describe his current research on understanding and manipulating the synthesis of carotenoids and vitamin E - both important antioxidants - in plants.

While the need is most urgent in developing nations, DellaPenna is a vocal advocate for improving the nutritional properties of staple crops to deliver a healthier, more balanced diet in wealthy nations.

As Swiss researchers Ingo Potrykus and Peter Beyer, the inventors of beta-carotene-enriched "golden rice", learned, the challenges are not only technical. Western activists have convinced many risk-averse Western consumers that genetically modified crops pose unacceptable threats to the environment, and to their health.

Prince Charles, heir to the British throne, and Britain's largest producer of organic foods, declared a decade ago that scientists were "entering realms that belong to God, and God alone" by meddling with crop genes.

The prince returned to his theme in August this year, warning that big agribusiness corporations and their GM crops would be "the absolute destruction of everything, and the classic way of ensuring that there is no food in the future". But, in a sign of changing times, some UK newspaper columnists lampooned the prince's views.

DellaPenna believes scientists need to do a better job of educating public. "The reality is that if you go into a supermarket, nearly every food has been genetically modified in some way," he says.

"Most of the produce - even organic produce - is mutant. Humans have been selecting for particular mutations for 10,000 years, and we have been using chemical and radiation mutagenesis for decades."

Organic misconceptions

Chemical mutagens and cobalt-60 radiation are very harsh mutagens, which typically cause dozens random mutations in seeds. "Breeders must pick through the mutants for traits they like, then try to get rid mid of many unwanted mutations as they can," DellaPenna says.

"Recombinant DNA technology is actually more precise - we can now determine exactly where a transgene has gone into a chromosome, what other genes are in that region, and assess the likelihood that there might be unintended consequence on nearby genes.

"There is a misconception out there that organic foods are safer than genetically engineered foods. My view is that we would have the best of both worlds if we can develop GE crops to resist pests, fungus and viral diseases, and other types of problems, and grow them with minimal pesticides - or even organically, without pesticides - but that's almost heresy."

DellaPenna says micronutrient deficiencies were a problem in industrialised nations at the beginning of the 19th century, and were corrected by adding the missing nutrients. Fortifying foods like breakfast cereals with iron and vitamins, and, more recently, folate and omega-3 fatty acids, remains common practice.

"But we can't do that in developing nations because of supply-chain problems," he says. "You can grow a variety of vegetables to provide a balanced diet, but that's simply unrealistic in most target populations, where staple crops account for between 50 to 95 per cent of total nutrient intake."

The obvious solution is to make the changes directly in the foods, so the solution is delivered pre-packaged in the seed, not by supplementation.

"We can deliver folate in rice, and vitamin E, which may also help stabilise lipids in the rice grain and inhibit it from going rancid. Vitamin E is required for good immune function, and for cell-membrane

DellaPenna says the required data are obtained by studying model systems to identify the genes involved in the various metabolic pathways. But in some cases, the approach will merely require directed breeding, using variant alleles of genes already present in the crop.

DellaPenna's team, and other research groups, have dissected the carotenoid biosynthetic pathway and identified the genes involved - their work underpinned the achievement of Beyer and Potrykus in
engineering "golden rice" to synthesise beta-carotene, using transgenes from bacteria and daffodil.

"Fifty per cent of the world's population lives on rice, and if you want to make them sufficient in vitamin A and folate, the best solution is to engineer these pathways directly into the grain," he says.

"But the bottom line is that we must improve the nutritional properties of our food crops as soon as we can, by whatever means we can."

Nutritional genomics

A US research project, led by Dr Edward Buckler of Cornell University's Institute of Genomic Diversity, has identified natural allelic variants in the lycopene epsilon cyclase (lycE) gene in maize, associated with a threefold difference in concentrations of provitamin A compounds in maize.

Researchers identified four natural polymorphisms that explained 58 per cent of the variation in levels of alpha and beta carotene, and beta cryptoxanthin in maize.

One of the lycE alleles decreases activity in one leg of a biosynthetic pathway, and directs more carbon into the other, resulting in higher levels of beta-carotene in maize kernels.

"It's a beautiful example of the interweaving of basic science and targeted breeding," DellaPenna says. "Some of these alleles are already present in late-stage breeding lines, so breeders can go in and select fourth-or fifth generation material to develop high provitamin A varieties."

DellaPenna says his research group has pioneered the concept of "nutritional genomics": as fully sequenced genomes become available for important crop species, it is apparent that many of the compounds researchers are interested in have dual functions.

Provitamin A is needed to prevent macular degeneration of the retina. "We initially worked on provitamin A compounds from the plant side - how they are made, and their role in photosynthesis."

In plants, they are involved in oxygen production, and in limiting oxidative damage.

"The third area we are working hard is using natural variation to help us how compounds are made and modified within the plants - for example, we can take petunia lines, cross them, then select in subsequent generations for genetic variation underlying particular biosynthetic pathways.

"We can do that for metabolites as well, by cloning quantitative trait loci (QTLs) in Arabidopsis. Many of those linkages are going to be important selection targets in crops - they increase levels of vitamin
E, specific carotenoids, and the bioavalability of minerals like iron.

"Iron is certainly the major limiting micronutrient in the human diet. One of the reasons for iron deficiency and anaemia in developing countries is that iron in plant tissues is much less bioavailable than in animal products.

"For example, 30 to 40 per cent of the total iron content of a hamburger might end up in the bloodstream, but if the equivalent amount were available in rice, maize or wheat, only 5 per cent would end up in the bloodstream, because other compounds in plants inhibit iron uptake.

"But there are also compounds in plants that stimulate iron uptake through the intestines. Using natural variation and QTLs to identify the genes involved in the Arabidopsis model system, we can investigate how the proteins or enzymes involved influence iron uptake by human intestinal epithelia cells in culture.

"In the longer term, we can move those genes into crops and they should have an enormous benefit on human nutrition, without changing the amount of iron in plants. If we could double or triple iron availability, it would have major benefits for people's ability to work, to increase their red cell counts, and improve their immune responses."

Metabolic bang-for-the-buck

DellaPenna says his team and others are still sifting through massive amounts of plant genomic data, to identify the genes involved in these metabolic pathways, and to determine how they evolved. He says plants actually have composite genomes derived from multiple endosymbiotic events during their evolution - for example, their acquisition of chloroplasts and mitochondria.

To date, his team has identified only single-gene variation influencing these metabolic pathways; it hopes to identify natural variants of transcription-factor genes that regulate entire pathways. Because transcription factors drive coordinated networks of scores to hundreds genes, they offer prospects for more metabolic bang-for-the-buck.

In terms of industrial applications, some plant groups specialise in synthesising novel compounds like morphine and other alkaloids.

"We can identify a shortlist of genes that might be involved in the synthesis pathway, then mass-spec all the compounds they produce," he says. "We're only scratching the surface of what is going on out there in the plant world. Much of the interesting variation has no visible effect on the phenotype of the plant - it's only apparent at the biochemical level. As the instruments get better, we're getting bigger
telescopes that allow us to see many more things."

The natural-variation approach relieves researchers of having to make assumptions about what is important. Mother Nature may not know what is best for humans, but she is at least telling researchers what is important, he says.

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