Enhancing Human Nutrition Through Genetics
Dr. Bill Park
*Introduction
-Traditional emphasis in medicine is on curing disease
-Now increasing amount of focus on disease prevention
-Healthy food does not do very much good unless people actually eat it
*Rice is World's Most Important Crop
-Rice is the model cereal
-Rice has small genome, which leads to easy transformation
-Rice also has well developed genetic maps and a suite of biotech tools to use
*Rice Processing Reduces Nutritional Quality
-Process: brown rice --> white rice = decreased dietary fiber and vitamins/minerals, increased glycemic index (bad)
*Disadvantages of Brown Rice
-Becomes rancid when stored
-Methods to counter these properties negatively affect the taste of the rice
*Golden Rice
-Genetically engineered to make precursor of vitamin A in endosperm
-Uses genes from bacteria and flowers
-Impressive technical achievement
-Level of vitamin A was initially very low
*Public Outcry Over GM Crops
-Greenpeace renews its opposition to GM rice
-Genetic novelty (inappropiate expression of allergens)
-Escape of transgenes into related weeds
-Displacing native varieties (reliable low input varieties are dependent on fertilizer and pesticides)
-Should people live in poverty and malnutrition just for genetic diversity?
-Would you buy golden rice for your family, or are there better ways to increase the amount of vitamin A in their diet?
*Need Thoughtful Analysis of Opportunities and Markets
-Good products to increase nutritional value for consumers must take into account:
4. Subjective factors, such as taste preference
*Making Health Food That People Will Actually Eat
-Need to take into consideration: cost, quality, convenience, subjective factors, and nutritional value
*Ideas Are Changing About What Constitutes A Healthy Diet
-New food pyramid has white rice in the 'use sparingly' category
-Brown rice remains in the 'use daily' category, but still is not a good product
-A product is needed with the nutritional benefits of brown rice and the convenience of white rice
*Research in Association with Corporate Partner and Plant Breeder
-Not biotech or research company
-Company discovered: unusual rice variety + special process --> brown rice that cooked in 10 minutes and did not become rancid
-Problems: very poor yield made product too expensive, some batches had no response to process
*'2+' Project
-Which genes are required to respond to process?
-Why did batches sometimes not work?
-Moved key genes into high yielding variety to ensure success everytime
*Critical Gene Likely Involved in Starch Synthesis
-Experts hypothesized that the special properties of the rice variety was due to variation in a gene involved in starch synthesis --> proved wrong
*Gene Discovery During Variety Development
-Did several crosses between wild type and '2+' quality rice and developed 300 different lines of rice
-Compared markers between high and low yielding species
-The critical gene is GBSS (makes amylase, which has to do with the cooking properties of rice)
-A single base change in GBSS is very important to '2+ Rice'
*Gene Expression and Regulation, Alternate Splicing Upstream Open Reading Frames
-snRNP = RNA protein complex that binds to the front end of an intron and splices it from the RNA
-In '2+' varieties, the base switch from G to T occurs in the snRNP binding site
-This causes the snRNP to bind and splice the mRNA in the wrong location, which alters the reading frame of the codons
-G-T mutation causes inefficient removal of GBSS leader intron
*Why Do Some Batches With Special Gene Not Respond to the '2+' Process?
-Effect of G/T polymorphism that influences GBSS mRNA processing is temperature dependent
-Splice sites shift in response to temperature
-18-32 degree range for AGTTATA splice site functions is physiologically relevant
-At 18 degrees C, the mutation has little or no effect on splicing, so these crops don't respond to the special method that produces the improved brown rice
-At 32 degrees C, the mutation takes effect and the reading frame is changed, so the crops respond well to the special method
-Growing proper selection in areas with consistent warm temperatures during grain development !!!!!!!!!!
-Using this knowledge could ensure they would get a crop that would respond to the special process so they could be sure that they would have enough rice to produce a new product
-Basically allowed them to produce new brown rice at low risk
*New Commercial Brown Rice Varieties
-First tailored for fast cooking non GM rice
-First in Europe and U.s. using molecular biology for development of new product with marker assisted selection
-Now have product on grocery store shelves across Europe, soon to U.S.
-Why it works as a product:
1. Had enhanced nutritional value of brown rice
2. Convenient with an only 10 minute cooking time
3. Costs less than other types of rice
4. Taste is preferred over other types of rice
5. Not genetically modified
*What If Special Variety Is Attacked By Plant Pathogen?
-DNA markers used to identify disease resistance genes
-These beneficial genes added to '2+' variety
-Now have higher yielding disease resistant rice tailored for cooking
-Changing process can dramatically change sensory scores
*Key Objective Is Optimal Combination Of Raw Material and Process
-Molecular biomaterials research
-Traditional approach - largely imperical (observations, cause and effect, little understanding of basis for findings), takes time, requires large quantities of material
-Fundamental approach - extremely complex and detailed (research of basic principles and mechanisms, looking to understand basis of results), poor understanding, lots of research required to know everything
-Dr. Park and his colleagues attempt to work inbetween traditional and fundamental approaches by looking at rice using polymer physics
-Cooked rice is composite polymer whose physical properties depend on: 1)the extent of the cross linking matrix, 2)the nature and strength of the filler, 3)the interactions between matrix and filler
-If we understand effects of genes and process we can look for optimal combination
-Slightly different versions of GBSS gene also explain other rice quality aspects
*Wider Application of Findings
-With new information concerning the GBSS mutation, it's possible to explain the difference between rice cooking qualities of many types of rice and to develop different rice types for different areas of the world
*Technology Transfer
-DNA markers screen lines from rice breeding programs
-Also using blast resistance genes
*Rice is Most Important Food Crop in Africa
-Starvation and hunger due to non-irrigated rice with poor yields
-Better way to enhance African nutrition - grow golden rice?
-Might be better to increase yields and allow people to keep native rice varieties
*NERICA - New Rice For Africa
-Cross between standard rice and wild rice from Africa
-Double and triple the yield under non-irrigated conditions, people have more to eat
-Problem: African farmers don't always like highest yielding NERICA lines because some local markets don't like grain quality of NERICA lines
-They often grow the lower yielding rice to sell at market, and use NERICA rice to feed their families
-Apparent transgressive segregation and recombination has been reported
-To see if genes were different, they examined series of African varieties and found that GBSS genes function the same in African rice as in other varieties
*Fundamentally More Useful to Encourage Golden Rice or Indigenous Rice?
-Working to set up collaboration between African breeding programs to boost economy, as they can produce a product at high yield that no one else can
-Path of creating healthy food has led to unexpected paths and continues to be an interesting journey