Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within-and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.Asian cultivated rice is grown worldwide and comprises the staple food for half of the global population. It is envisaged that by the year 2035 1 feeding this growing population will necessitate that an additional 112 million metric tons of rice be produced on a smaller area of land, using less water and under more fluctuating climatic conditions, which will require that future rice cultivars be higher yielding and resilient to multiple abiotic and biotic stresses. The foundation of the continued improvement of rice cultivars is the rich genetic diversity within domesticated populations and wild relatives [2][3][4] . For over 2,000 years, two major types of O. sativa-O. sativa Xian group (here referred to as Xian/Indica (XI) and also known as , Hsien or Indica) and O. sativa Geng Group (here referred to as Geng/Japonica (GJ) and also known as , Keng or Japonica)-have historically been recognized [5][6][7] . Varied degrees of post-reproductive barriers exist between XI and GJ rice accessions 8 ; this differentiation between XI and GJ rice types and the presence of different varietal groups are well-documented at isozyme and DNA levels 6,9 . Two other distinct groups have also been recognized using molecular markers 10 ; one of these encompasses the Aus, Boro and Rayada ecotypes from Bangladesh and India (which we term the circum-Aus group (cA)) and the other comprises the famous Basmati and Sadri aromatic varieties (which we term the circum-Basmati group (cB)).Approximately 780,000 rice accessions are available in gene banks worldwide 11 . To enable the more efficient use of these accessions in future rice improvement, the Chinese Academy of Agricultural Sciences, BGI-Shenzhen and International Rice Research Institute sequenced over 3,000 rice genomes (3K-RG) as part of the 3,000 Rice Genomes Project 12. Here we present analyses of genetic variation in the 3K-RG that focus on important aspects of O. sativa diversity, single nucleotide polymorphisms (SNPs) and structural variation (deletions, duplications, inversions and translocations). We also construct a species pangenome consisting of 'core...

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide1, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified 2, despite analysis of more than 9,000 cases3. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

No abstract

SummaryAdversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

Male Sterile2 (MS2) is predicted to encode a fatty acid reductase required for pollen wall development in Arabidopsis (Arabidopsis thaliana). Transient expression of MS2 in tobacco (Nicotiana benthamiana) leaves resulted in the accumulation of significant levels of C16 and C18 fatty alcohols. Expression of MS2 fused with green fluorescent protein revealed that an amino-terminal transit peptide targets the MS2 to plastids. The plastidial localization of MS2 is biologically important because genetic complementation of MS2 in ms2 homozygous plants was dependent on the presence of its amino-terminal transit peptide or that of the Rubisco small subunit protein amino-terminal transit peptide. In addition, two domains, NAD(P)H-binding domain and sterile domain, conserved in MS2 and its homologs were also shown to be essential for MS2 function in pollen exine development by genetic complementation testing. Direct biochemical analysis revealed that purified recombinant MS2 enzyme is able to convert palmitoyl-Acyl Carrier Protein to the corresponding C16:0 alcohol with NAD(P)H as the preferred electron donor. Using optimized reaction conditions (i.e. at pH 6.0 and 30°C), MS2 exhibits a K(m) for 16:0-Acyl Carrier Protein of 23.3 ± 4.0 μm, a V(max) of 38.3 ± 4.5 nmol mg⁻¹ min⁻¹, and a catalytic efficiency/K(m) of 1,873 M⁻¹ s⁻¹. Based on the high homology of MS2 to other characterized fatty acid reductases, it was surprising that MS2 showed no activity against palmitoyl- or other acyl-coenzyme A; however, this is consistent with its plastidial localization. In summary, genetic and biochemical evidence demonstrate an MS2-mediated conserved plastidial pathway for the production of fatty alcohols that are essential for pollen wall biosynthesis in Arabidopsis.

Mature pollen is covered by durable cell walls, principally composed of sporopollenin, an evolutionary conserved, highly resilient, but not fully characterized, biopolymer of aliphatic and aromatic components. Here, we report that ABORTED MICROSPORES (AMS) acts as a master regulator coordinating pollen wall development and sporopollenin biosynthesis in Arabidopsis thaliana. Genome-wide coexpression analysis revealed 98 candidate genes with specific expression in the anther and 70 that showed reduced expression in ams. Among these 70 members, we showed that AMS can directly regulate 23 genes implicated in callose dissociation, fatty acids elongation, formation of phenolic compounds, and lipidic transport putatively involved in sporopollenin precursor synthesis. Consistently, ams mutants showed defective microspore release, a lack of sporopollenin deposition, and a dramatic reduction in total phenolic compounds and cutin monomers. The functional importance of the AMS pathway was further demonstrated by the observation of impaired pollen wall architecture in plant lines with reduced expression of several AMS targets: the abundant pollen coat protein extracellular lipases (EXL5 and EXL6), and CYP98A8 and CYP98A9, which are enzymes required for the production of phenolic precursors. These findings demonstrate the central role of AMS in coordinating sporopollenin biosynthesis and the secretion of materials for pollen wall patterning.

Anther cuticle and pollen exine act as protective envelopes for the male gametophyte or pollen grain, but the mechanism underlying the synthesis of these lipidic polymers remains unclear. Previously, a tapetum-expressed CYP703A3, a putative cytochrome P450 fatty acid hydroxylase, was shown to be essential for male fertility in rice (Oryza sativa L.). However, the biochemical and biological roles of CYP703A3 has not been characterized. Here, we observed that cyp703a3-2 caused by one base insertion in CYP703A3 displays defective pollen exine and anther epicuticular layer, which differs from Arabidopsis cyp703a2 in which only defective pollen exine occurs. Consistently, chemical composition assay showed that levels of cutin monomers and wax components were dramatically reduced in cyp703a3-2 anthers. Unlike the wide range of substrates of Arabidopsis CYP703A2, CYP703A3 functions as an in-chain hydroxylase only for a specific substrate, lauric acid, preferably generating 7-hydroxylated lauric acid. Moreover, chromatin immunoprecipitation and expression analyses revealed that the expression of CYP703A3 is directly regulated by Tapetum Degeneration Retardation, a known regulator of tapetum PCD and pollen exine formation. Collectively, our results suggest that CYP703A3 represents a conserved and diversified biochemical pathway for in-chain hydroxylation of lauric acid required for the development of male organ in higher plants.

As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality.