Systems Genetic Validation of the SNP-Metabolite Association in Rice Via Metabolite-Pathway-Based Phenome-Wide Association Scans

We have produced a draft sequence of the rice genome for the most widely cultivated subspecies in China, Oryza sativa L. ssp. indica, by whole-genome shotgun sequencing. The genome was 466 megabases in size, with an estimated 46,022 to 55,615 genes. Functional coverage in the assembled sequences was 92.0%. About 42.2% of the genome was in exact 20-nucleotide oligomer repeats, and most of the transposons were in the intergenic regions between genes. Although 80.6% of predicted Arabidopsis thaliana genes had a homolog in rice, only 49.4% of predicted rice genes had a homolog in A. thaliana. The large proportion of rice genes with no recognizable homologs is due to a gradient in the GC content of rice coding sequences.

Plant metabolites are important to world food security in terms of maintaining sustainable yield and providing food with enriched phytonutrients. Here we report comprehensive profiling of 840 metabolites and a further metabolic genome-wide association study based on ∼6.4 million SNPs obtained from 529 diverse accessions of Oryza sativa. We identified hundreds of common variants influencing numerous secondary metabolites with large effects at high resolution. We observed substantial heterogeneity in the natural variation of metabolites and their underlying genetic architectures among different subspecies of rice. Data mining identified 36 candidate genes modulating levels of metabolites that are of potential physiological and nutritional importance. As a proof of concept, we functionally identified or annotated five candidate genes influencing metabolic traits. Our study provides insights into the genetic and biochemical bases of rice metabolome variation and can be used as a powerful complementary tool to classical phenotypic trait mapping for rice improvement.