NATURE BIOTECHNOLOGY VOLUME 30 NUMBER 1 JANUARY 2012 105 RESOURCE Asian cultivated rice (Oryza sativa) is thought to have been domesti- cated from divergent populations of Asian wild rice, O. rufipogon and O. nivara, >10,000 years ago 1,2 . During domestication, rice has under- gone significant phenotypic changes in grain size, color, shattering, seed dormancy and tillering. For decades, geneticists have used quanti- tative trait locus mapping to localize the major causative genes respon- sible for these traits, yielding a dozen trait-related genes in cultivated rice (for example, sh4, rc and prog1) 3–6 . Additionally, a recent genome- wide association study using genome-wide SNP data for 517 Chinese landraces identified loci that may be associated with 14 agronomic traits 7 . However, quantitative trait locus and gene mapping is labor intensive and time consuming, taking years to construct segregating populations and requiring intensive phenotyping and genotyping. Association mapping is also prone to missing excellent alleles because the favorable alleles tend to be rare and are difficult to detect during regular association analyses 8 . A more recent report tried to identify artificially selected genes 9 , but the strategy of pooling many accessions (a strain identified by an International Rice Research Institute (IRRI) accession number) together and using shallow sequencing coverage provided limited variation data for rice. If a comprehensive catalog of genome variation in both cultivated and wild rice were available, it would greatly facilitate the identification of functional variations in elite varieties by comparing genomic variation in an elite variety with data from controls. Dense variation data will also be useful for marker-assisted breeding and gene mapping of rice. RESULTS Sequencing and mapping Cultivated rice is classified into two major subspecies of O. sativa (indica and japonica) and is further subdivided into genetically dif- ferentiated groups, including Glaszmann’s six groups (I to VI) 10 and Garris et al.’s five groups (indica, aus, aromatic, temperate japonica and tropical japonica) 11 . We selected 40 cultivated rice accessions to represent all of the major groups of Asian cultivated rice (Supplementary Table 1), including 11 tropical japonica (TRJ), 8 temperate japonica (TEJ) and 6 aromatic (ARO) that belong to japonica rice, and 4 aus (AUS) and 9 indica (IND) that belong to indica rice (Supplementary Table 1). In addition, we sampled one accession each from groups III and IV, proposed by Glaszmann 10 , which were not included in a previous population study 11 . Among these cultivars, 29 are considered to be landraces and 11 are improved varieties. To strictly control the quality of our sequencing and SNP calling, we also included the Nipponbare strain, which was used to generate the reference rice genome sequence 12 . For wild rice samples, Resequencing 50 accessions of cultivated and wild rice yields markers for identifying agronomically important genes Xun Xu 1–3,12 , Xin Liu 2,12 , Song Ge 4,12 , Jeffrey D Jensen 5,12 , Fengyi Hu 6,12 , Xin Li 1,12 , Yang Dong 1,12 , Ryan N Gutenkunst 7 , Lin Fang 2 , Lei Huang 3,4 , Jingxiang Li 2 , Weiming He 2,8 , Guojie Zhang 1,2,4 , Xiaoming Zheng 3,4 , Fumin Zhang 3 , Yingrui Li 2 , Chang Yu 2 , Karsten Kristiansen 2,9 , Xiuqing Zhang 2 , Jian Wang 2 , Mark Wright 10 , Susan McCouch 10 , Rasmus Nielsen 1,9,11 , Jun Wang 2,9 & Wen Wang 1 Rice is a staple crop that has undergone substantial phenotypic and physiological changes during domestication. Here we resequenced the genomes of 40 cultivated accessions selected from the major groups of rice and 10 accessions of their wild progenitors (Oryza rufipogon and Oryza nivara) to >15 × raw data coverage. We investigated genome-wide variation patterns in rice and obtained 6.5 million high-quality single nucleotide polymorphisms (SNPs) after excluding sites with missing data in any accession. Using these population SNP data, we identified thousands of genes with significantly lower diversity in cultivated but not wild rice, which represent candidate regions selected during domestication. Some of these variants are associated with important biological features, whereas others have yet to be functionally characterized. The molecular markers we have identified should be valuable for breeding and for identifying agronomically important genes in rice. 1 CAS-Max Planck Junior Research Group on Evolutionary Genomics, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences (CAS), Kunming, China. 2 BGI-Shenzhen, Shenzhen, China. 3 Graduate University of Chinese Academy Sciences, Beijing, China. 4 State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing, China. 5 School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. 6 Food Crops Research Institute, Yunnan Academy of Agricultural Sciences, Kunming, China. 7 Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA. 8 South China University of Technology, Guangdong, China. 9 Department of Biology, University of Copenhagen, Copenhagen, Denmark. 10 Department of Plant Breeding & Genetics, Cornell University, Ithaca, New York, USA. 11 Departments of Integrative Biology and Statistics, University of California, Berkeley, USA. 12 These authors contributed equally to this work. Correspondence should be addressed to W.W. (wwang@mail.kiz.ac.cn) or J.W. (wangj@genomics.org.cn) or R.N. (rasmus_nielsen@berkeley.edu). Received 3 June; accepted 25 October; published online 11 December 2011; doi:10.1038/nbt.2050 npg © 2012 Nature America, Inc. All rights reserved.