Source: NORTH CAROLINA STATE UNIV submitted to NRP
THE GENETIC IMPROVEMENT OF PLANT DERIVED PHYTOCHEMICALS AND PHYTONUTRIENTS IN FRUITS AND VEGETABLE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0219061
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 30, 2008
Project End Date
Sep 30, 2013
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
NORTH CAROLINA STATE UNIV
(N/A)
RALEIGH,NC 27695
Performing Department
Horticultural Science
Non Technical Summary
Diet has a significant impact on human health. Some estimates project that a third of all cancer deaths in the United States could be avoided through the appropriate modification of diet. The consumption of fruits and vegetables is related to reduced rates of tumor initiation and progress, occurrence of cardiovascular disease, urinary tract infections, rheumatoid arthritis, diabetes, macular degeneration, gastric ulcers, and other disorders. A number of health promoting compounds (phytochemicals) in fruits and vegetables such as glucosinolates, alpha and beta-carotene, lutein, lycopene, alpha-tocopherol, ascorbate, folic acid, phytosterols such as beta-sitosterol and stigmasterol; triterpene esters; phenolic molecules such as anthocyanins, flavonols, proanthocyanidins, ellagitannins, and phenolic acids; and phytonutrients such as calcium and selenium have been suggested to act in a protective manner through a variety of different mechanisms. Efforts to encourage the public to consume greater quantities of fruits and vegetables have to date shown limited success. In 1991, the non-profit organization "Produce for Better Health" and the National Cancer Institute initiated the "5 a Day for Better Health" program to promote healthy eating through increased fruit and vegetable consumption. However, results from surveys conducted from 1992 to 2002 suggested that average daily fruit intake among persons over 2 years of age remained the same (1.6 servings) and that average daily vegetable consumption declined from 3.4 to 3.2 servings during the same period. In 2005, approximately 33% of the US adult population surveyed consumed fruit two or more times per day, and only 27% ate vegetables three or more times per day. Additionally, more than 60% of North Carolina adults are overweight or obese, significantly above the national average. More than 77% of North Carolina adults do not eat the recommended five fruits or vegetables per day. Physical inactivity and unhealthy eating combined are the second leading preventable cause of death in North Carolina and the nation at large, and both increase the risk of heart disease, certain types of cancer, diabetes, high blood pressure, stroke and obesity. In addition to encouraging the public to consume greater quantities of fruits and vegetables through programs dedicated to increasing awareness, a second approach to combating chronic disease would be to enhance the concentration of health promoting compounds in fruits and vegetables through conventional plant breeding techniques. Unfortunately, a number of obstacles exist. These health promoting compounds are difficult to measure precise evaluations require expensive instrumentation and specialized technical expertise. The current analyses are generally too time-consuming and cost prohibitive for most breeding programs. The development of molecular markers associated with genes' that impact the variability of health promoting compounds in fruit and vegetables crops would speed the development of enhanced fruits and vegetables and result in economic benefit to growers and health benefits to consumers.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2011120108110%
2011122108110%
2011440108110%
2011460108110%
2021120108110%
2021460108110%
2041120108110%
2041122108110%
2041440108110%
2041460108110%
Goals / Objectives
The research will focus on the genetics and stability of health-promoting phytochemicals and phytonutrients (e.g. glucosinolates, beta carotene, lutein, lycopene, tocopherols, ascorbate, folic acid, phytosterols such as beta sitosterol and stigmasterol; triterpene esters; phenolic molecules such as anthocyanins, flavonols, proanthocyanidins, ellagitannins, phenolic acids, and selenium) in fruits and vegetables of economic importance to North Carolina consumers and producers. Multi-year, comprehensive surveys of the variability of these compounds in primary and secondary gene pools (elite germplasm and non-cultivated relatives) will be conducted and high throughput assays for phytochemical analysis will be developed. Four breeding programs in the Department of Horticulture at North Carolina State University (blueberry, strawberry, tomato, and watermelon) and a fifth program at the USDA facility in Charleston, SC (cruciferous vegetables) will collaborate and provide germplasm for these surveys. Priority will be given to blueberry, tomato and cruciferous vegetables, as appropriate populations for these surveys have already been established. Analysis will be conducted using HPLC and LC-MS in the Brown lab during 2009-2011 and will represent the most extensive survey of phytochemicals to date in blueberry. Molecular markers will be developed that are associated with variation in the plants secondary metabolomic profile, particularly with those compounds in the glucosinolate, flavonoid, and carotenoid biochemical pathways. Priority will be given to developing single-nucleotide polymorphic (SNP) markers within candidate genes of interest. The project will collaborate with existing breeding programs to identify and/or assemble appropriate populations for the genetic mapping of both structural and regulatory factors associated with variation. Linking a plant's secondary metabolomic profile to molecular markers, either through the use of evenly-spaced, genome wide marker scans or by utilizing select candidate genes with putative functions, will allow for a closer examination of how these plants accumulate phytochemicals and will also provide molecular markers that will ultimately lead to fruits and vegetables with enhanced phytochemical profiles.
Project Methods
Over 600 genotypes of 3-year-old blueberry are currently located at Piedmont Research Station, Salisbury N.C. This population includes elite germplasm, hybrids, progenies and open pollinated progenies. A broad representative sample of diploid, tetraploid and hexaploid species will be evaluated over 3 years. Blueberry fruit will be harvested from each of 600 plants at the Piedmont Research Station, Salisbury, NC, at a uniform statge. Sub-samples will be labeled and processed for extraction based on the chemical properties and polarity of the desired phytochemical class. More polar compounds such as the phenolic acids ascorbic acid will be extracted using water as a main inorganic solvent. Less polar compounds such as the anthocyanins and proanthocyanidins will be extracted for quantitative analysis using a mixture of organic and inorganic solvents followed by high-speed centrifugation to separate extracts containing target compounds from pellets. Carotenoids and fat-soluble vitamins, the least polar compounds will be extracted using non polar solvents such as ethanol and saponified. Assaying samples for phytochemical content will require utilizing multiple platforms. The confirmation of compound identity will be performed using HP Liquid Chromatography coupled with Quadrupole Time of Flight mass spectrometer with MS/MS capability. The accuracy of this procedure allows exact mass measurements of small molecules such as quercetin, and of much larger molecules such as proanthocyanidins. The estimation of compound concentration will be performed using Ultra Performance Liquid Chromatography that allows for faster and more cost efficient quantification of compounds. Analysis will be conducted during 2009-2011 and will represent the most extensive survey of phytochemicals to date in blueberry. Surveys of carotenoid and flavonoid variability will also be conducted using 32 diverse tomato genotypes. These 32 genotypes represent cultivated and wild. Surveys will be conducted at the Research stations at Mills River and Salisbury, NC, in 2010 and 2011. Phytochemical analysis of tomatoes will be as described previously for blueberries. Candidate gene sequences will be identified through a variety of techniques. Where draft genomic sequences are available (Blueberry), the sequences will represent the best candidates based on either homology or predicated function, or conserved domains of interest. Where draft genomic sequences are not available, candidate genes will be identified utilizing degenerate primers based on sequences of related or model crops. The identified candidate gene sequences will be used to design primers (PRIMER3). A panel of accessions will be used to identify and validate SNPs. SNP assays will be developed through a number of vendors (ABI Biosystems and Illumina.). The populations described previously will be genotyped with the SNP assays and several software programs will be utilized to determine the statistical significance of detected associations between markers and traits of interest (SAS, NTsys, STRUCTURE, and TASSEL).

Progress 10/01/11 to 09/30/12

Outputs
OUTPUTS: 1)The first saturated genetic map of broccoli has been produced using the newly released Illumina Brassica SNP array. These SNPs, originally developed from canola have allowed for the localization of previously identified QTLs associated with glucosinolates, carotenoids, and minerals and provide a link to the model crop Arabidopsis that allows for identification of candidate genes. The genetic map of broccoli spans 836 cM along all 9 linkage groups with an average spacing of 2.3 cM. results will be shared in 2013 at PAG and the annual brassica meetings. 2)A single QTL (Gene) was identified in broccoli that contributes approximately half of the genetic variation observed in Lutein in broccoli. Results have been shared with the Monsanto Company 3) The first genetic population structure of blueberry has been accomplished utilizing a subset of the 43,000 markers developed by our lab. Results were shared at the annual ASHS 2012. 4) The blueberry genomic sequence has been made available to the general public through our website (vaccinium.org) PARTICIPANTS: The General Mills Corporation has provided in-kind support for the project by providing genotyping of the broccoli population using the Illumina SNP array through an independent lab. All costs for this were provided by General Mills. Mike Grusak (USDA/Baylor) provided phenotyping of micronutrient (Ca, Zn, Mg, Fe, and others) at no cost. The Monsanto Company has provided matching funds for the continuation of the lutein research in broccoli. Dr Jeannie Rowland, USDA-Beltsville has provided funding through a sponsored project agreement to continue the genomic work and gene discovery of health promoting compounds in blueberry. TARGET AUDIENCES: The Brassica research community will benefit from the development of the first brassica oleracea SNP map. Any researcher seeking to identify a candidate gene in brassica oleracea will be able to utilize this map to identify corresponding genomic scaffolds in canola and corresponding candidate genes in Arabidopsis. Gene discovery will be facilitated. Senior citizens suffering from AMD and cataracts and health conscious consumers wishing to avoid these health concerns later in life will benefit from broccoli that produces twice the levels of lutein found in commercially available broccoli. PROJECT MODIFICATIONS: we are observing that increases in lutein in broccoli appear to be correlated with increases in chlorophyl (an antioxidant)and vitamin K (phylloquinone). As all three of these health related compounds are also involved in photosynthesis, understanding the driving force among these compounds could lead to plants with higher levels of all three compounds and also shed light on modifying photosynthesis activity in plants. The relationship among these 3 compounds will be explored in greater detail using the genomic tools developed this year.

Impacts
1) The SNP based genetic linkage map of Brassica oleracea provides a new mechanism to align the broccoli genome to the genomes of canola and Arabidopsis thereby transferring the knowledge of the model crop (Arabidopsis) to a crop of economic importance (broccoli). 2) Identification of single gene associated with lutein led to an active sponsored collaboration with Monsanto that will develop broccoli with enhanced levels of lutein and combat age-related macular degeneration. 3) Blueberry molecular markers have been provided to ongoing efforts by USDA (Beltsville and Corvalis)(as well as international collaborators in NZ and the UK)to saturate the diploid and genetic linkage maps of blueberry and to identify QTLs associated with anthocyanin concentration by collaborators at UF.

Publications

  • Guzman, I., Yousef, G.G., and Brown, A.F. (2012) Simultaneous extraction and quantitation of carotenoids, chlorophylls, and tocopherols in Brassica vegetables. Journal of Agricultural and Food Chemistry. 60(29):7238-7244.


Progress 10/01/10 to 09/30/11

Outputs
OUTPUTS: Broccoli: 150 inbred lines of broccoli population VI-158 x BNC were grown and harvested at Salisbury NC in Fall 2010 (the second season). Extraction and analysis of glucosinolates, carotenoids, tocopherols, and micronutrients were conducted over the winter. A new protocol for the simultaneous extraction of carotenoids, tocopherols and chlorophyll was developed. A single molecular marker associated with half of the genetic variation of lutein and beta-carotene was discovered that mapped to the same location in this population in 2009 and 2010. Lutein levels from this population are higher than anything previously reported in broccoli. Reports were presented at the American Society for Horticultural Science and the Phytochemical Society of North America. Spring 2011 planting of broccoli with multiple harvest dates identified the impact that latter planting has on indole but not aliphatic glucosinolates. Blueberry: Thirteen hundred cultivated blueberry varieties were harvested at Salisbury NC in Fall 2010 (the second season). Extraction and analysis of anthocyanins was completed for material harvested in 2009. Significant quantitative and qualitative variation was observed among the material. Results were presented at International anthocyanin workshops and at the North Carolina blueberry growers association. 43,000 blueberry SSR markers were identified including markers associated with major genes in the anthocyanin pathway. Two hundred of these markers were provided to collaborators saturating the consenus Results presented at the American Society of Horticultural Science. Peaches: A second season of 4 cultivars of peaches were harvested from 4 locations in North and South Carolina. Peel and fruit of peaches from both years were analyzed for phenolic compounds and anthocyanins. PARTICIPANTS: Dr. Mary Ann Lila (NCSU), Dr. Jim Ballington (NCSU)and Dr. Ann Lorraine (UNCC) participated in the phytochemical analysis of blueberries. Dr. Lisa Rowland and Dr. Nahla Bassil (both USDA) collaborated on diversity study of blueberry. Dr. Dilip Panthee and Dr. Peneople Perkins-Veazie (both NCSU) participated in tomato phytochemical and marker development. Dr. Perkins-Veazie also participated in peach project along with Dr. Ksenji Gasic (Clemson and Dr. Mike Parker (NCSU). Dr. Mark Farnham (USDA) contributed to broccoli work. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
A new protocol for the simultaneous extraction of carotenoids, tocopherols and chlorophyll from brassica vegetables was developed that reduces the time and cost of analyzing broccoli and cauliflower samples. This allows for a more efficent development of improved cultivars. The SSR markers developed through the genomic sequencing project have been incorporated into the consensus blueberry genetic linkage map and more than the doubled the number of markers on the map.

Publications

  • No publications reported this period


Progress 10/01/09 to 09/30/10

Outputs
OUTPUTS: In the field, the second and final year of a phytochemical GXE analysis of peaches was harvested from locations in North and South Carolina. The broccoli population (150 F2:F3 plants ) was grown and harvested in spring and fall of 2010. A UPLC protocol for the simultaneous analysis of carotenoids and tocopherols in broccoli was developed. Three hundred additional DNA sequence-based markers were screened in our lab corresponding to genes in the carotenoid, glucosinolate, and fatty acid biosynthetic pathway. The broccoli population has been advanced (inbred) and additional 2 generation. The second season of a multi-year analysis of blueberry phytochemicals were also harvested and analyzed. Over 1300 genotypes of blueberries were included for what appears to be the largest most exhaustive study of this type done in blueberry. An additional 4GB of DNA sequence for the blueberry draft genomic sequence was generated in the last year and has identified candidate gene sequences that correspond to known genes in the phenylpropanoid/flavonoid biosynthetic pathway. We have identified over 20,000 new SSR sequences in blueberry and contributed along with collaborators to the development of several thousand SNP sequences. A website has been developed in collaboration with Washington State University to house the blueberry genomic sequence. We have accepted a gift from the Monsanto corporation in the form of several thousand accessions of cabbage from an inactive breeding program. We have initiated a program for testing germination of material and for evaluating select material for phytochemical content. PARTICIPANTS: PARTICIPANTS: Dr. Mary Ann Lila (NCSU), Dr. Jim Ballington (NCSU)and Dr. Ann Lorraine (UNCC) participated in the phytochemical analysis of blueberries. Dr. Lisa Rowland and Dr. Nahla Bassil (both USDA) collaborated on diversity study of blueberry. Dr. Perkins-Veazie participated in peach project along with Dr. Ksenji Gasic (Clemson and Dr. Mike Parker (NCSU). Dr. Mark Farnham (USDA) contributed to broccoli work. A graduate student, Yang Bian was added to project and has worked with Dr. Ballington to develop core subset of blueberry for diversity estimation. TARGET TARGET AUDIENCES: In the narrow sense the target audience is the research communities associated with the various crops, however, in a broader sense; the target is the consumer who will eventually have access to fruits and vegetables with enhanced health benefits. PROJECT MODIFICATIONS: A cabbage germplasm collection has been accepted as a gift from the Monsanto corporation includes material from early selections to late generation inbreds. This generous and fortuitous gift will necessitate that cabbage take the place of other crops (e.g.strawberry) for which we had originally hoped to include in our research but were not able to obtain funding or interested collaborators.

Impacts
The development of the new UPLC protocol for simultaneous analysis of carotenoids and tocopherols in broccoli will significantly speed up the accurate analysis of these compounds and the development of superior varieties of broccoli with enhanced levels of Lutein, Beta-carotene and alpha tocopherol. The increased blueberry DNA sequence material and identification of candidate genes, SSR and SNP markers will dramatically impact all aspects of molecular improvement of of blueberry through both marker assisted selection and genetic engineering.

Publications

  • Bassil, N., B. Gilmore, T. Mockler, L. Wilhelm, J. Olmstead, A. Brown, and L. Rowland. SNP Mining in Blueberry Using Illumina GAII Sequencing. 107th ASHS Aug 2 2010, Palm Desert CA.
  • Yousef, G., A. Brown, F Mbeunkui, M. Grace, K. Patel, J. Ballington, A. Loraine, and M. Lila. Variation in Anthocyanins in Blueberry (Vaccinium spp.) and Implications for Genetics Research and Human Health. 107th ASHS Aug 2 2010, Palm Desert CA.
  • Yousef, G., F. Mbeunkui, M. Grace, K. Patel, J. Ballington, A. Loraine, M. Lila, and A. Brown. Diversity and abundance of Anthocyanins in Blueberry (Vaccinium spp.) species with different multiploidy levels. Proc. North American Blueberry Research and extension Workers Conference. Kalamazoo MI, July 28, 2010.
  • Reid, W., C.R. Brouwer, G.M. Wright, M. Burke, A. Natarajan, and A. Brown. Characterization Of Repeats In A Draft Sequence Of The Blueberry Genome. Proc Plant and Animal Genome Meetings XIX. January 15-19, 2011.
  • Wright, G.M, M. Burke, A. Raja, C. Brouwer, R. Reid, and A. Brown. Construction Of A Blueberry (Vaccinium corymbosium) Draft Genomic Sequence Using A Multiple Platform Approach: An Update. Proc Plant and Animal Genome Meetings XIX. January 15-19, 2011.


Progress 10/30/08 to 09/30/09

Outputs
OUTPUTS: The blueberry sequencing project has progressed over the past year and produced data that has been mined for candidate gene sequences associated with flavonoid and anthocyanin biosynthesis. Gene sequences from grape (Vitis) were used to identify structural and regulatory gene candidates in blueberry. Similarity scores based on predicted protein structure ranged from .45 (stilbene synthase) to .95 (chalcone synthase) with most scores greater than 85 percent. These results will be presented at the Plant and Animal Genome meetings, 2010. Primers have been designed for these sequences and DNA obtained from mapped blueberry populations. DNA has been obtained from over 600 blueberry accessions currently being grown at the Piedmont Research Station (PRS) at Salisbury, NC. Fruit from these same accessions were harvested and is currently being assayed for phytochemical content. In addition, 300 putative blueberry microsatellite markers have been identified and primers designed. Primers that display polymorphism will be used to assay diversity among blueberry accessions at PRS and will be added to existing diploid and tetraploid genetic linkage maps. Fruit from four varieties of Peach have been harvested from 2 locations in North Carolina and 2 locations in South Carolina as part of 2 year collaboration with Clemson University to study variability in phytochemical content of Peach. The study will be completed in the coming year. Fruit and DNA from 200 tomato accessions were obtained in collaboration with Dr Dilip Panthee to study phytochemical content in tomato. Funding has been obtained through a USDA specialty crop block grant to develop and design molecular markers that can be used to improve tomato phytochemical content. One hundred and twenty-two F2:3 families of broccoli were harvested from the PRS in 2009. Initial metabolomic analysis of the parents suggests that over 300 individual secondary metabolites are distinct enough to allow for QTL mapping in the progenies. One hundred and twenty five primer pairs corresponding to known genes in broccoli have been designed based on published sequences in GenBank. To date, 70% of the primers designed have amplified a single PCR product. These PCR products will be sequenced, SNPs identified and placed on a existing genetic linkage map. Eventually these genes will be tested for association with the metabolite biosynthesis. PARTICIPANTS: Dr. Mary Ann Lila (NCSU), Dr. Jim Ballington (NCSU)and Dr. Ann Lorraine (UNCC) participated in the phytochemical analysis of blueberries. Dr. Lisa Rowland and Dr. Nahla Bassil (both USDA) collaborated on diversity study of blueberry. Dr. Dilip Panthee and Dr. Peneople Perkins-Veazie (both NCSU) participated in tomato phytochemical and marker development. Dr. Perkins-Veazie also participated in peach project along with Dr. Ksenji Gasic (Clemson and Dr. Mike Parker (NCSU). Dr. Mark Farnham (USDA) contributed to broccoli work. A graduate student, Yang Bian was added to project and has worked with Dr. Ballington to develop core subset of blueberry for diversity estimation. TARGET AUDIENCES: In the narrow sense the target audience is the research communities associated with the various crops, however, in a broader sense; the target is the consumer who will eventually have access to fruits and vegetables with enhanced health benefits. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The initial outputs of this abbreviated year lay the ground work for determining how much of the observable variation in phytochemical content in blueberry, peach, tomato, and broccoli are heritable and therefore amendable to breeding. The markers designed in blueberry and broccoli will have a direct impact on breeding of these crops by producing the first gene specific molecular markers in either crop. The use of the blueberry genomic sequence information to identify specific phytochemical genes demonstrates the utility of this approach in identifying blueberry genes of interest.

Publications

  • No publications reported this period