Berkeleylactones S-T, novel 16-membered macrolides isolated from the endophytic fungus Penicillium egyptiacum.

The fungus Penicillium egyptacum has been reported as a producer of the 16-membered macrolide antibiotic A26771B. In this study, two new berkeleylactone analogues, berkeleylactones S-T (1-2), were isolated from P. egyptiacum. Their structures were determined by the analyses of 1D- and 2D-NMR data, HRESIMS, and chemical derivatization. 1 is the first example of berkeleylactone analogue possessing a glucose moiety, whose absolute configuration was elucidated by acid hydrolysis followed by derivatization and LC-MS analysis. No antibacterial activity against Bacillus subtilis and Streptococcus salivarius was found within the range of 0-100 µM for compounds 1-2.

Two pairs of 2-pyrone enantiomers and a benzophenone analogue from the endophytic fungus Penicillium egyptiacum.

Four new 2-pyrone derivatives, two pairs of enantiomers, (±)-egypyrone A [(±)-1] and (±)-egypyrone B [(±)-2], together with a new benzophenone analogue, orbiophenone B (3), were isolated from the endophytic fungus Penicillium egyptiacum. The enantiomeric mixtures (±)-1 and (±)-2 were separated through chiral HPLC, respectively. Their structures were elucidated by extensive analysis of spectroscopic data and the absolute configuration was determined by comparing the optical rotation of structurally similar molecule. Subsequently, the cytotoxic activities of (±)-1, (±)-2, and 3 against the U87 cell line were tested and no activity was observed at a concentration of 10 µM.

Image-based visualization of stents in mechanical thrombectomy for acute ischemic stroke: Preliminary findings from a series of cases.

BACKGROUND: Mechanical thrombectomy is the most effective treatment for great cerebral artery embolization within a set time window. Typically, an arteriogram does not show the localization of the stent after release and whether a thrombus is captured or not. Thus, improving the visualization of a stent in interventional therapy will be helpful for clinicians. AIM: To analyze stent imaging findings to enhance clinicians' understanding of a special circumstance, wherein a Solitaire AB retrievable stent was visible during the imaging of a thrombus capture that improved the success rate of stent-based mechanical thrombectomy. METHODS: This was a retrospective study with four acute ischemic stroke (AIS) patients who underwent stent-based mechanical thrombectomy. RESULTS: Patient 1 was a 64-year-old man admitted after 5 h of confusion; angiography revealed basilar artery occlusion. We inserted a stent into the left posterior cerebral artery-P2 segment and visualized the expanded stent that successfully captured a thrombus. Patient 2 was a 74-year-old man admitted with confusion, which lasted approximately 3 h. Angiography revealed a left middle cerebral artery (MCA)-M1 segment occlusion. A stent was deployed in the distal M2 segment, and we could visualize the stent by capturing the thrombus. Patient 3 was a 74-year-old woman admitted after experiencing left hemiplegia for 3 h. We deployed a stent at the distal right MCA-M2 segment, and the developing stent captured a large thrombus. Patient 4 was an 82-year-old man who presented with confusion for 3 h. A developing stent was placed in the distal left MCA-M1 segment, which captured a large thrombus and several fragmented thrombi. CONCLUSION: To the best of our knowledge, this is the first report of stent imaging in patients with AIS. We demonstrated the usefulness and substantial potential of stent imaging in stent-based mechanical thrombectomy for AIS.

Multiple domestications of Asian rice.

The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.

Baicalein ameliorates Alzheimer's disease via orchestration of CX3CR1/NF-κB pathway in a triple transgenic mouse model.

Alzheimer's disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1ß and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.

Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

L-Carnitine Alleviates the Myocardial Infarction and Left Ventricular Remodeling through Bax/Bcl-2 Signal Pathway.

Purpose: L-carnitine (LC) is considered to have good therapeutic potential for myocardial infarction (MI), but its mechanism has not been clarified. The aim of the study is to elucidate the cardioprotective effects of LC in mice following MI and related mechanisms. Methods: ICR mice were treated with LC for 2 weeks after induction of MI with ligation of left anterior descending artery. Electrocardiographic (ECG) recording and echocardiography were used to evaluate cardiac function. H&E staining, TTC staining, and Masson staining were performed for morphological analysis and cardiac fibrosis. ELISA and immunofluorescence were utilized to detect biomarkers and inflammatory mediators. The key proteins in the Bax/Bcl-2 signaling pathway were also examined by Western blot. Results: Both echocardiography and histological measurement showed an improvement in cardiac function and morphology. Biomarkers such as LDH, NT-proBNP, cTnT, and AST, as well as the inflammatory cytokines IL-1ß, IL-6, and TNF-α, were decreased in plasma of mice receiving LC treatment after myocardial injury. In addition, the expression of α-SMA as well as the key proteins in the Bax/Bcl-2 signaling pathway in cardiac myocardium were much lower in mice with LC treatment compared to those without after MI. Conclusions: Our data suggest that LC can effectively ameliorate left ventricular (LV) remodeling after MI, and its beneficial effects on myocardial function and remodeling may be attributable at least in part to anti-inflammatory and inhibition of the Bax/Bcl-2 apoptotic signaling pathway.

Safety and Efficacy of Ginkgo-Damole and Nitroglycerin or Sodium Nitroprusside on Hypertensive Cerebropathies: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the safety and efficacy of ginko-damole combined with nitroglycerin or unitary sodium nitroprusside on hypertensive cerebropathy. METHODS: Four Chinese databases (VIP, CBM, Wanfang database, and CNKI database) and three English databases (Cochrane, PubMed, and EMBASE) were used to screen randomised controlled trials (RCTs) on treatments of hypertensive cerebropathy using both ginko-damole and nitroglycerin or unitary sodium nitroprusside. Outcomes included clinical effect, blood pressure after treatment, and adverse effects. These indicators were then analysed statistically using the RevMan 5.3 and Stata 12.0 software. RESULTS: Altogether, 16 RCTs including 1507 patients with hypertensive cerebropathy were included in the present meta-analysis, of which, 755 patients treated with combined ginko-damole and nitroglycerin were included in the observation group and 752 patients treated with sodium nitroprusside were included in the control group. The curative effect of the observation group was significantly better than that of the control group (RR: 1.115 [1.077, 1.155], p < 0.05). DBPs of the observation and control groups were both lower after treatment, and no significant difference was observed between the observation and control groups (MD: -1.072 [-2.578, 0.434], p > 0.05). SBPs in the observation group were significantly lower than those in the control group (MD: -2.842 [-5.222, -0.462], p < 0.05). The probability of adverse response in both groups did not differ significantly (RR: 0.752 [0.412, 1.374], p > 0.05). CONCLUSION: Compared with sodium nitroprusside, the combined ginkgo-damole and nitroglycerin could better control blood pressure in patients with hypertensive cerebropathy and showed enhanced clinical effects and improved safety. However, due to poor quality of the included studies, results of the present meta-analysis should be confirmed by more stringent RCTs.

Divergence in flowering time is a major component contributing to reproductive isolation between two wild rice species (Oryza rufipogon and O. nivara).

It is of critical importance for our understanding of speciation process to determine the forms of reproductive isolation and their relative importance in species divergence. Oryza nivara and O. rufipogon are direct ancestors of Asian cultivated rice and a progenitor-daughter species pair. Investigating the reproductive isolation between them provides insights into plant speciation and helps understanding of the rice domestication. Here, we quantitatively measured the major components of reproductive isolation between the two species based on common garden and crossing experiments for three pairs of sympatric populations in Nepal, Cambodia and Laos. We revealed significant differences in the flowering times between species pairs, with O. nivara flowering much earlier than O. rufipogon. A very weak reduction in seed set but no reduction in F1 viability and fertility were detected for the crosses between species relative to those within species. Moreover, we detected asymmetrical compatibility between species and found that emasculation significantly decreased pollination success in O. nivara but not in O. rufipogon. Our study demonstrates that the divergence between O. nivara and O. rufipogon is maintained almost entirely by the difference in flowering times and suggests that differential flowering times contribute to both habitat preferences and reproductive isolation between species.

Resequencing 545 ginkgo genomes across the world reveals the evolutionary history of the living fossil.

As Charles Darwin anticipated, living fossils provide excellent opportunities to study evolutionary questions related to extinction, competition, and adaptation. Ginkgo (Ginkgo biloba L.) is one of the oldest living plants and a fascinating example of how people have saved a species from extinction and assisted its resurgence. By resequencing 545 genomes of ginkgo trees sampled from 51 populations across the world, we identify three refugia in China and detect multiple cycles of population expansion and reduction along with glacial admixture between relict populations in the southwestern and southern refugia. We demonstrate multiple anthropogenic introductions of ginkgo from eastern China into different continents. Further analyses reveal bioclimatic variables that have affected the geographic distribution of ginkgo and the role of natural selection in ginkgo's adaptation and resilience. These investigations provide insights into the evolutionary history of ginkgo trees and valuable genomic resources for further addressing various questions involving living fossil species.

Parallel Speciation of Wild Rice Associated with Habitat Shifts.

The occurrence of parallel speciation strongly implies the action of natural selection. However, it is unclear how general a phenomena parallel speciation is since it was only shown in a small number of animal species. In particular, the adaptive process and mechanisms underlying the process of parallel speciation remain elusive. Here, we used an integrative approach incorporating population genomics, common garden, and crossing experiments to investigate parallel speciation of the wild rice species Oryza nivara from O. rufipogon. We demonstrated that O. nivara originated multiple times from different O. rufipogon populations and revealed that different O. nivara populations have evolved similar phenotypes under divergent selection, a reflection of recurrent local adaptation of ancient O. rufipogon populations to dry habitats. Almost completed premating isolation was detected between O. nivara and O. rufipogon in the absence of any postmating barriers between and within these species. These results suggest that flowering time is a "magic" trait that contributes to both local adaptation and reproductive isolation in the origin of wild rice species. Our study thus demonstrates a convincing case of parallel ecological speciation as a consequence of adaptation to new environments.

Syntheses, crystal-solution structures and magnetic properties of a series of decanuclear heterometallic [LnCoCo] (Ln = Eu, Gd, Tb, Dy) clusters.

Four unprecedented decanuclear heterometallic [Ln2CoII4CoIII4] clusters based on a diethanolamine ligand (H2dea), namely [Eu2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (1), [Gd2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (2), [Tb2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (3) and [Dy2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (4) were synthesized through a facile solution method. Single-crystal X-ray diffraction analyses reveal that complexes 1-4 consist of a [Ln2CoII4CoIII4] core, which is constructed by bridging a quasi-double cuboidal [Ln2CoII2CoIII2] core with two [CoIICoIII] units. Electrospray ionization mass spectrometry (ESI-MS) using methanol solution reveals that complexes 1-4 are stable in the solution, and the clusters undergo three different substitution reactions (Cl- replaced by OH-, OH- replaced by CH3O- and HCOO- replaced by OH-/CH3O-) at the same time in the ionization state. Magnetic susceptibilities reveal ferromagnetic couplings within complexes 3 and 4, and the magnetocaloric effect (MCE) for 2 was also evaluated and the maximum entropy change (-ΔSm) value reaches 16.3 J kg-1 K-1 at about 3 K and 5 T.

Genome-wide association study of rice grain width variation.

Seed size is variable within many plant species, and understanding the underlying genetic factors can provide insights into mechanisms of local environmental adaptation. Here we make use of the abundant genomic and germplasm resources available for rice (Oryza sativa) to perform a large-scale genome-wide association study (GWAS) of grain width. Grain width varies widely within the crop and is also known to show climate-associated variation across populations of its wild progenitor. Using a filtered dataset of >1.9 million genome-wide SNPs in a sample of 570 cultivated and wild rice accessions, we performed GWAS with two complementary models, GLM and MLM. The models yielded 10 and 33 significant associations, respectively, and jointly yielded seven candidate locus regions, two of which have been previously identified. Analyses of nucleotide diversity and haplotype distributions at these loci revealed signatures of selection and patterns consistent with adaptive introgression of grain width alleles across rice variety groups. The results provide a 50% increase in the total number of rice grain width loci mapped to date and support a polygenic model whereby grain width is shaped by gene-by-environment interactions. These loci can potentially serve as candidates for studies of adaptive seed size variation in wild grass species.

Predictive models of adjuvant chemotherapy for patients with stage ii colorectal cancer: A retrospective study.

BACKGROUND: It remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy. METHODS: The current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation. RESULTS: In the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05). CONCLUSIONS: According to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.

OsCOL16, encoding a CONSTANS-like protein, represses flowering by up-regulating Ghd7 expression in rice.

Flowering time is an important agronomic trait that coordinates the plant life cycle with regional adaptability and thereby impacts yield potentials for cereal crops. The CONSTANS (CO)-like gene family plays vital roles in the regulation of flowering time. CO-like proteins are typically divided into four phylogenetic groups in rice. Several genes from groups I, III, and IV have been functionally characterized, though little is known about the genes of group II in rice. We report the functional characterization in rice of a constitutive floral inhibitor, OsCOL16, encoding a group-II CO-like protein that delays flowering time and increases plant height and grain yield. Overexpression of OsCOL16 resulted in late heading under both long-day and short-day conditions. OsCOL16 expression exhibits a diurnal oscillation and serves as a transcription factor with transcriptional activation activity. We determined that OsCOL16 up-regulates the expression of the floral repressor Ghd7, leading to down-regulation of the expression of Ehd1, Hd3a, and RFT1. Moreover, genetic diversity and evolutionary analyses suggest that remarkable differences in flowering times correlate with two major alleles of OsCOL16. Our combined molecular biology and phylogeographic analyses revealed that OsCOL16 plays an important role in regulating rice photoperiodic flowering, allowing for environmental adaptation of rice.

Time-cumulated blood pressure exposure and incident impairment of glucose tolerance and diabetes mellitus.

BACKGROUND: With the marked increase in the prevalence of diabetes mellitus, it was the purpose of our study to assess a potential association of time-cumulated exposure to systolic (CumSBP) and of diastolic blood pressure (CumDBP) with onset of impaired glucose tolerance and diabetes mellitus. METHODS: The prospective investigation included participants of the longitudinal Kailuan Study with three baseline examinations in 2006-2007, 2008-2009 and 2010-2011, re-examination in 2012-2013, and no diabetes mellitus at baseline. Cumulative blood pressure (BP) was calculated as cumBP = [(BP1 + BP2)/2 × time1-2] + [(BP2 + BP3)/2 × time2-3]. Based on cumSBP, the study population was stratified into four groups (cumSBP < 480mmHgxyear;n = 15,339; 480mmHgxyear ≤ cumSBP < 520mmHgxyear;n = 7214; 520mmHgxyears ≤ cumSBP < 560mmHgxyears;n = 5675; and cumSBP ≥ 560mmHgxyears;n = 10,576). RESULTS: After adjusting for demographic, anthropomorphic, biochemical, socioeconomic and lifestyle parameters and as compared with the first group, the second, third and fourth group showed a significantly higher incidence of diabetes (P-trend < 0.001;hazard ratio (HR);95% confidence interval (CI):1.28(1.08,1.51),1.54(1.29,1.84), and 2.33(1.98,2.73), respectively), higher incidence of impairment of glucose tolerance (P-trend < 0.001;HR;95% CI1.17(1.02,1.33), 1.43(1.25,1.64), and 2.09(1.85,2.37), respectively), and higher incidence of diabetes developing out of an impairment of glucose tolerance (P-trend < 0.001;HR;95% CI:1.22(0.97,1.54),1.47(1.16,1.86), and 2.01(1.62,2.50), respectively). An increase in cumSBP by 10 mmHg/year or an increase in cumDBP by 5 mmHg/year was associated with a hazard ratio of incident diabetes of 1.04 (95% CI:1.03,1.04) and 1.02(1.02,1.03), respectively, with a hazard ratio of incident impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and 1.03(95% CI:1.02,1.03), respectively, and with a hazard ratio of incident diabetes developing from impairment of glucose tolerance of 1.04(95% CI:1.03,1.04) and 1.03(95% CI:1.02,1.03), respectively. CONCLUSIONS: Time-cumulated exposure to elevated blood pressure was significantly associated with an elevated incidence of impaired glucose tolerance and diabetes.

Ideal cardiovascular health and incident hypertension: The longitudinal community-based Kailuan study.

Ideal cardiovascular health (CVH) has been defined by the American Heart Association as the absence of disease and presence of 7 key health factors. Since it is unknown whether cumulative exposure to CVH reduces the risk of developing arterial hypertension, we prospectively examined the potential association between cumulative CVH (cumCVH) score (except for blood pressure metrics) and incident hypertension.Of the 101,510 participants with an age range of 18 to 98 years in this longitudinal community-based Kailuan study, our cohort included those 15,014 participants without hypertension at baseline and who had follow-up examinations 2, 4, and 6 years later. CumCVH was calculated as the summed CVH score for each examination multiplied by the time between the 2 examinations (points × year). Based on the cumCVH score, the study population was stratified into groups of <44 points, 44 to 48 points, 49 to 54 points, 55 to 59 points, and ≥60 points.Incidence of hypertension ranged from 16.76% in the lowest cumCVH category to 11.52% in the highest cumCVH category. After adjusting for age, sex, education level, income level, high-sensitivity C-reactive protein concentration, uric acid concentration, resting heart rate, parental history of hypertension at baseline, and medication usage before the third follow-up examination, participants in the highest cumCVH category had a significantly reduced risk of incident hypertension compared with those in the lowest cumCVH category (adjusted odds ratio 0.60, 95% confidence interval 0.50-0.71). For every increase in category based on the cumCVH score, the risk of hypertension decreased by approximately 2% (odds ratio 0.98, 95% confidence interval 0.97-0.98). The effect was consistent across sex and age groups.A higher cumCVH score is associated with a lower risk of incident hypertension.

Nonfunctional alleles of long-day suppressor genes independently regulate flowering time.

Due to the remarkable adaptability to various environments, rice varieties with diverse flowering times have been domesticated or improved from Oryza rufipogon. Detailed knowledge of the genetic factors controlling flowering time will facilitate understanding the adaptation mechanism in cultivated rice and enable breeders to design appropriate genotypes for distinct preferences. In this study, four genes (Hd1, DTH8, Ghd7 and OsPRR37) in a rice long-day suppression pathway were collected and sequenced in 154, 74, 69 and 62 varieties of cultivated rice (Oryza sativa) respectively. Under long-day conditions, varieties with nonfunctional alleles flowered significantly earlier than those with functional alleles. However, the four genes have different genetic effects in the regulation of flowering time: Hd1 and OsPRR37 are major genes that generally regulate rice flowering time for all varieties, while DTH8 and Ghd7 only regulate regional rice varieties. Geographic analysis and network studies suggested that the nonfunctional alleles of these suppression loci with regional adaptability were derived recently and independently. Alleles with regional adaptability should be taken into consideration for genetic improvement. The rich genetic variations in these four genes, which adapt rice to different environments, provide the flexibility needed for breeding rice varieties with diverse flowering times.

Widespread and Adaptive Alterations in Genome-Wide Gene Expression Associated with Ecological Divergence of Two Oryza Species.

Ecological speciation is a common mechanism by which new species arise. Despite great efforts, the role of gene expression in ecological divergence and speciation is poorly understood. Here, we conducted a genome-wide gene expression investigation of two Oryza species that are evolutionarily young and distinct in ecology and morphology. Using digital gene expression technology and the paired-end RNA sequencing method, we obtained 21,415 expressed genes across three reproduction-related tissues. Of them, approximately 8% (1,717) differed significantly in expression levels between the two species and these differentially expressed genes are randomly distributed across the genome. Moreover, 62% (1,064) of the differentially expressed genes exhibited a signature of directional selection in at least one species. Importantly, the genes with differential expression between species evolved more rapidly at the 5' flanking sequences than the genes without differential expression relative to coding sequences, suggesting that cis-regulatory changes are likely adaptive and play an important role in the ecological divergence of the two species. Finally, we showed evidence of significant differentiation between species in phenotype traits and observed that genes with differential expression were overrepresented with functional terms involving phenotypic and ecological differentiation between the two species, including reproduction- and stress-related characteristics. Our findings demonstrate that ecological speciation is associated with widespread and adaptive alterations in genome-wide gene expression and provide new insights into the importance of regulatory evolution in ecological speciation in plants.

Population genetic structure of Oryza rufipogon and Oryza nivara: implications for the origin of O. nivara.

Ecological speciation plays a primary role in driving species divergence and adaptation. Oryza rufipogon and Oryza nivara are two incipient species at the early stage of speciation with distinct differences in morphology, life history traits and habitat preference, and therefore provide a unique model for the study of ecological speciation. However, the population genetic structure of the ancestral O. rufipogon has been controversial despite substantial study, and the origin of the derivative O. nivara remains unclear. Here, based on sequences of 10 nuclear and two chloroplast loci from 26 wild populations across the entire geographic ranges of the two species, we conducted comprehensive analyses using population genetics, phylogeography and species distribution modelling (SDM) approaches. In addition to supporting the two previously reported major subdivisions, we detected four genetically distinct groups within O. rufipogon and found no correlation between the genetic groups and either species identity or geographical regions. The SDM clearly showed substantial change in the distribution range of O. rufipogon in history, demonstrating that the repeated extinction and colonization of local populations due to multiple glacial-interglacial cycles during the Quaternary was most likely the main factor shaping the confounding population genetic structure of O. rufipogon. Moreover, we found significant differences between the two species in climate preferences, suggestive of an important role for climatic factors in the adaptation, persistence and expansion of O. nivara. Finally, based on the genetic pattern and dynamics of the O. nivara populations, we hypothesize that O. nivara might have independently originated multiple times from different O. rufipogon populations.