The telomere-to-telomere (T2T) genome of Peucedanum praeruptorum Dunn provides insights into the genome evolution and coumarin biosynthesis.

BACKGROUND: Traditional Chinese medicine has used Peucedanum praeruptorum Dunn (Apiaceae) for a long time. Various coumarins, including the significant constituents praeruptorin (A-E), are the active constituents in the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies have attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and thus the development of better breeding strategies. RESULTS: A telomere-to-telomere (T2T) genome was assembled for P. praeruptorum by combining PacBio HiFi, ONT ultra-long, and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes with genome completeness >98%. Comparative genomic analysis suggested that P. praeruptorum experienced 2 whole-genome duplication events. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the COSY and cytochrome P450 genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins. CONCLUSIONS: A T2T genome for P. praeruptorum was obtained, providing molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds.

Integrating genomic and multiomic data for Angelica sinensis provides insights into the evolution and biosynthesis of pharmaceutically bioactive compounds.

Angelica sinensis roots (Angelica roots) are rich in many bioactive compounds, including phthalides, coumarins, lignans, and terpenoids. However, the molecular bases for their biosynthesis are still poorly understood. Here, an improved chromosome-scale genome for A. sinensis var. Qinggui1 is reported, with a size of 2.16 Gb, contig N50 of 4.96 Mb and scaffold N50 of 198.27 Mb, covering 99.8% of the estimated genome. Additionally, by integrating genome sequencing, metabolomic profiling, and transcriptome analysis of normally growing and early-flowering Angelica roots that exhibit dramatically different metabolite profiles, the pathways and critical metabolic genes for the biosynthesis of these major bioactive components in Angelica roots have been deciphered. Multiomic analyses have also revealed the evolution and regulation of key metabolic genes for the biosynthesis of pharmaceutically bioactive components; in particular, TPSs for terpenoid volatiles, ACCs for malonyl CoA, PKSs for phthalide, and PTs for coumarin biosynthesis were expanded in the A. sinensis genome. These findings provide new insights into the biosynthesis of pharmaceutically important compounds in Angelica roots for exploration of synthetic biology and genetic improvement of herbal quality.

CRISPR/Cas9-mediated seamless gene replacement in protoplasts expands the resistance spectrum to TMV-U1 strain in regenerated Nicotiana tabacum.

CRISPR/Cas-based genome editing is now extensively used in plant breeding and continues to evolve. Most CRISPR/Cas current applications in plants focus on gene knock-outs; however, there is a pressing need for new methods to achieve more efficient delivery of CRISPR components and gene knock-ins to improve agronomic traits of crop cultivars. We report here a genome editing system that combines the advantages of protoplast technologies with recent CRISPR/Cas advances to achieve seamless large fragment insertions in the model Solanaceae plant Nicotiana tabacum. With this system, two resistance-related regions of the N' gene were replaced with homologous fragments from the N'alata gene to confer TMV-U1 resistance in the T0 generation of GMO-free plants. Our study establishes a reliable genome-editing tool for efficient gene modifications and provides a detailed description of the optimization process to assist other researchers adapt this system for their needs.

Whole-genome sequencing of diverse wheat accessions uncovers genetic changes during modern breeding in China and the United States.

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.

Differential SW16.1 allelic effects and genetic backgrounds contributed to increased seed weight after soybean domestication.

Although seed weight has increased following domestication from wild soybean (Glycine soja) to cultivated soybean (Glycine max), the genetic basis underlying this change is unclear. Using mapping populations derived from chromosome segment substitution lines of wild soybean, we identified SW16.1 as the causative gene underlying a major quantitative trait locus controlling seed weight. SW16.1 encodes a nucleus-localized LIM domain-containing protein. Importantly, the GsSW16.1 allele from wild soybean accession N24852 had a negative effect on seed weight, whereas the GmSW16.1 allele from cultivar NN1138-2 had a positive effect. Gene expression network analysis, reverse-transcription quantitative polymerase chain reaction, and promoter-luciferase reporter transient expression assays suggested that SW16.1 regulates the transcription of MT4, a positive regulator of seed weight. The natural variations in SW16.1 and other known seed weight genes were analyzed in soybean germplasm. The SW16.1 polymorphism was associated with seed weight in 247 soybean accessions, showing much higher frequency of positive-effect alleles in cultivated soybean than in wild soybean. Interestingly, gene allele matrix analysis of the known seed weight genes revealed that G. max has lost 38.5% of the G. soja alleles and that most of the lost alleles had negative effects on seed weight. Our results suggest that eliminating negative alleles from G. soja led to a higher frequency of positive alleles and changed genetic backgrounds in G. max, which contributed to larger seeds in cultivated soybean after domestication from wild soybean. Our findings provide new insights regarding soybean domestication and should assist current soybean breeding programs.

Integrated multi-omics analysis provides insights into genome evolution and phosphorus deficiency adaptation in pigeonpea (Cajanus cajan).

Pigeonpea (Cajanus cajan) is an important legume food crop and plays a crucial role in a secure food supply in many developing countries. Several previous studies have suggested that pigeonpea has great potential for phosphorus (P) deficiency tolerance, but little is known about the underlying mechanism. In this study, the physiological and molecular responses of pigeonpea roots to phosphate (Pi) starvation were investigated through integrating phenotypic, genomic, transcriptomic, metabolomic, and lipidomic analyses. The results showed that low-Pi treatment increased total root length, root surface area, and root acid phosphatase activity, and promoted the secretion of organic acids (e.g. citric acids, piscidic acids, and protocatechuic acids) and the degradation of phospholipids and other P-containing metabolites in the roots of pigeonpea. Consistent with the morphological, physiological, and biochemical changes, a large number of genes involved in these Pi-starvation responses were significantly upregulated in Pi-deficient pigeonpea roots. Among these Pi-starvation response genes upregulated by low-Pi treatment, four gene families were expanded through recent tandem duplication in the pigeonpea genome, namely phosphate transporter 1 (PHT1), phosphoethanolamine/phosphocholine phosphatase (PECP), fasciclin-like arabinogalactan protein (FLA), and glutamate decarboxylase (GAD). These gene families may be associated with Pi uptake from the soil, phospholipid recycling, root morphological remodeling, and regulation of organic acid exudation. Taken together, our results suggest that pigeonpea employs complex Pi-starvation responses to strengthen P acquisition and utilization during low-Pi stress. This study provides new insights into the genome evolution and P deficiency adaptation mechanism of pigeonpea.

Critical metabolic pathways and SAD/FADs, WRI1s, and DGATs cooperate for high-oleic acid oil production in developing oil tea (Camellia oleifera) seeds.

Oil tea trees produce high-quality edible oils with desirably high oleic acid (18:1) and low linoleic (18:2) and linolenic (18:3) fatty acid (FA) levels, but limited understanding of tea oil biosynthesis and regulation has become a significant obstacle for the breeding of high-yield and -quality oil tea varieties. By integrating metabolite and transcriptome analyses of developing oil tea seeds, we dissected the critical metabolic pathways, including glycolysis, fatty acid, and triacylglycerol (TAG) biosynthesis, as well as genes essential for tea seed oil production. Two plastidic stearoyl-acyl carrier protein desaturases (CoSAD1 and 2) and two endoplasmic reticulum-localized FA desaturases (CoFAD2 and 3) were functionally characterized as responsible for high 18:1 and low 18:2 and 18:3 proportions in tea oils. Two diacylglycerol O-acyltransferases (CoDGAT1 and 2) that may prefer to synthesize 18:1-TAG were functionally characterized and might be also important for high 18:1-TAG production. The highly expressed CoWRI1a and b were identified and characterized as activators of glycolysis and regulators of directing source carbon flux into FA biosynthesis in developing oil tea seeds. The upregulated CoSADs with downregulated CoFAD2 and CoFAD3 at the late seed developmental stages mainly accounted for high 18:1 levels. Two CoDGATs might be responsible for assembling TAGs with oleoyl acyl chains, whilst two CoWRI1s regulated carbons from parental sources, partitioning into oil production in oil tea embryo sinks. This study provides a deep understanding of the biosynthesis of tea seed oils and information on genes that may be used as molecular markers to breed oil tea varieties with higher oil yield and quality.

Whole-genome resequencing of the wheat A subgenome progenitor Triticum urartu provides insights into its demographic history and geographic adaptation.

Triticum urartu is the progenitor of the A subgenome in tetraploid and hexaploid wheat. Uncovering the landscape of genetic variations in T. urartu will help us understand the evolutionary and polyploid characteristics of wheat. Here, we investigated the population genomics of T. urartu by genome-wide sequencing of 59 representative accessions collected around the world. A total of 42.2 million high-quality single-nucleotide polymorphisms and 3 million insertions and deletions were obtained by mapping reads to the reference genome. The ancient T. urartu population experienced a significant reduction in effective population size (Ne) from ∼3 000 000 to ∼140 000 and subsequently split into eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations during the Younger Dryas period. A map of allelic drift paths displayed splits and mixtures between different geographic groups, and a strong genetic drift towards hexaploid wheat was also observed, indicating that the direct donor of the A subgenome originated from northwestern Syria. Genetic changes were revealed between the eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations in genes orthologous to those regulating plant development and stress responses. A genome-wide association study identified two single-nucleotide polymorphisms in the exonic regions of the SEMI-DWARF 37 ortholog that corresponded to the different T. urartu ecotype groups. Our study provides novel insights into the origin and genetic legacy of the A subgenome in polyploid wheat and contributes a gene repertoire for genomics-enabled improvements in wheat breeding.

Tea plant roots respond to aluminum-induced mineral nutrient imbalances by transcriptional regulation of multiple cation and anion transporters.

BACKGROUND: Tea is one of the most popular non-alcoholic beverages in the world for its flavors and numerous health benefits. The tea tree (Camellia sinensis L.) is a well-known aluminum (Al) hyperaccumulator. However, it is not fully understood how tea plants have adapted to tolerate high concentrations of Al, which causes an imbalance of mineral nutrition in the roots. RESULTS: Here, we combined ionomic and transcriptomic profiling alongside biochemical characterization, to probe the changes of metal nutrients and Al responsive genes in tea roots grown under increasing concentrations of Al. It was found that a low level of Al (~ 0.4 mM) maintains proper nutrient balance, whereas a higher Al concentration (2.5 mM) compromised tea plants by altering micro- and macro-nutrient accumulation into roots, including a decrease in calcium (Ca), manganese (Mn), and magnesium (Mg) and an increase in iron (Fe), which corresponded with oxidative stress, cellular damage, and retarded root growth. Transcriptome analysis revealed more than 1000 transporter genes that were significantly changed in expression upon Al exposure compared to control (no Al) treatments. These included transporters related to Ca and Fe uptake and translocation, while genes required for N, P, and S nutrition in roots did not significantly alter. Transporters related to organic acid secretion, together with other putative Al-tolerance genes also significantly changed in response to Al. Two of these transporters, CsALMT1 and CsALS8, were functionally tested by yeast heterologous expression and confirmed to provide Al tolerance. CONCLUSION: This study shows that tea plant roots respond to high Al-induced mineral nutrient imbalances by transcriptional regulation of both cation and anion transporters, and therefore provides new insights into Al tolerance mechanism of tea plants. The altered transporter gene expression profiles partly explain the imbalanced metal ion accumulation that occurred in the Al-stressed roots, while increases to organic acid and Al tolerance gene expression partly explains the ability of tea plants to be able to grow in high Al containing soils. The improved transcriptomic understanding of Al exposure gained here has highlighted potential gene targets for breeding or genetic engineering approaches to develop safer tea products.

Genomic regions controlling yield-related traits in spring wheat: a mini review and a case study for rainfed environments in Australia and China.

A genome-wide association study (GWAS) was performed in six environments to identify major or consistent alleles responsible for wheat yield traits in Australia and North China where rainfed farming system is adopted. A panel of 228 spring wheat varieties were genotyped by double digest restriction-site associated DNA genotyping-by-sequencing. A total of 223 significant marker-trait association (MTAs) and 46 candidate genes for large- or consistent-effect MTAs were identified. The results were compared with previous studies based on a mini-review of 23 GWAS analyses on wheat yield. A phenomenon seldom reported in previous studies was that MTAs responsible for the trait tended to cluster together at certain chromosome segments, and many candidate genes were in the form of gene clusters. Although linkage disequilibrium (LD) might contribute to the co-segregation of the regions, it also suggested that marker-assisted selection (MAS) or transgenic method targeting a single gene might not be as effective as MAS targeting a larger genomic region where all the genes or gene clusters underlying play important roles.

Differential microRNA expression, microRNA arm switching, and microRNA:long noncoding RNA interaction in response to salinity stress in soybean.

BACKGROUND: Soybean is a major legume crop with high nutritional and environmental values suitable for sustainable agriculture. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are important regulators of gene functions in eukaryotes. However, the interactions between these two types of ncRNAs in the context of plant physiology, especially in response to salinity stress, are poorly understood. RESULTS: Here, we challenged a cultivated soybean accession (C08) and a wild one (W05) with salt treatment and obtained their small RNA transcriptomes at six time points from both root and leaf tissues. In addition to thoroughly analyzing the differentially expressed miRNAs, we also documented the first case of miRNA arm-switching (miR166m), the swapping of dominant miRNA arm expression, in soybean in different tissues. Two arms of miR166m target different genes related to salinity stress (chloroplastic beta-amylase 1 targeted by miR166m-5p and calcium-dependent protein kinase 1 targeted by miR166m-3p), suggesting arm-switching of miR166m play roles in soybean in response to salinity stress. Furthermore, two pairs of miRNA:lncRNA interacting partners (miR166i-5p and lncRNA Gmax_MSTRG.35921.1; and miR394a-3p and lncRNA Gmax_MSTRG.18616.1) were also discovered in reaction to salinity stress. CONCLUSIONS: This study demonstrates how ncRNA involves in salinity stress responses in soybean by miRNA arm switching and miRNA:lncRNA interactions. The behaviors of ncRNAs revealed in this study will shed new light on molecular regulatory mechanisms of stress responses in plants, and hence provide potential new strategies for crop improvement.

Genome-wide identification of seed storage protein gene regulators in wheat through coexpression analysis.

Only a few transcriptional regulators of seed storage protein (SSP) genes have been identified in common wheat (Triticum aestivum L.). Coexpression analysis could be an efficient approach to characterize novel transcriptional regulators at the genome-scale considering the correlated expression between transcriptional regulators and target genes. As the A genome donor of common wheat, Triticum urartu is more suitable for coexpression analysis than common wheat considering the diploid genome and single gene copy. In this work, the transcriptome dynamics in endosperm of T. urartu throughout grain filling were revealed by RNA-Seq analysis. In the coexpression analysis, a total of 71 transcription factors (TFs) from 23 families were found to be coexpressed with SSP genes. Among these TFs, TuNAC77 enhanced the transcription of SSP genes by binding to cis-elements distributed in promoters. The homolog of TuNAC77 in common wheat, TaNAC77, shared an identical function, and the total SSPs were reduced by about 24% in common wheat when TaNAC77 was knocked down. This is the first genome-wide identification of transcriptional regulators of SSP genes in wheat, and the newly characterized transcriptional regulators will undoubtedly expand our knowledge of the transcriptional regulation of SSP synthesis.

Clinical Characteristics and Risk of Diabetic Complications in Data-Driven Clusters Among Type 2 Diabetes.

Background: This study aimed to cluster newly diagnosed patients and patients with long-term diabetes and to explore the clinical characteristics, risk of diabetes complications, and medication treatment related to each cluster. Research Design and Methods: K-means clustering analysis was performed on 1,060 Chinese patients with type 2 diabetes based on five variables (HbA1c, age at diagnosis, BMI, HOMA2-IR, and HOMA2-B). The clinical features, risk of diabetic complications, and the utilization of elven types of medications agents related to each cluster were evaluated with the chi-square test and the Tukey-Kramer method. Results: Four replicable clusters were identified, severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). In terms of clinical characteristics, there were significant differences in blood pressure, renal function, and lipids among clusters. Furthermore, individuals in SIRD had the highest prevalence of stages 2 and 3 chronic kidney disease (CKD) (57%) and diabetic peripheral neuropathy (DPN) (67%), while individuals in SIDD had the highest risk of diabetic retinopathy (32%), albuminuria (31%) and lower extremity arterial disease (LEAD) (13%). Additionally, the difference in medication treatment of clusters were observed in metformin (p = 0.012), α-glucosidase inhibitor (AGI) (p = 0.006), dipeptidyl peptidase 4 inhibitor (DPP-4) (p = 0.017), glucagon-like peptide-1 (GLP-1) (p <0.001), insulin (p <0.001), and statins (p = 0.006). Conclusions: The newly diagnosed patients and patients with long-term diabetes can be consistently clustered into featured clusters. Each cluster had significantly different patient characteristics, risk of diabetic complications, and medication treatment.

Comparative genomics analysis of Pediococcus acidilactici species.

Pediococcus acidilactici is a reliable bacteriocin producer and a promising probiotic species with wide application in the food and health industry. However, the underlying genetic features of this species have not been analyzed. In this study, we performed a comprehensive comparative genomic analysis of 41 P. acidilactici strains from various ecological niches. The bacteriocin production of 41 strains were predicted and three kinds of bacteriocin encoding genes were identified in 11 P. acidilactici strains, namely pediocin PA-1, enterolysin A, and colicin-B. Moreover, whole-genome analysis showed a high genetic diversity within the population, mainly related to a large proportion of variable genomes, mobile elements, and hypothetical genes obtained through horizontal gene transfer. In addition, comparative genomics also facilitated the genetic explanation of the adaptation for host environment, which specify the protection mechanism against the invasion of foreign DNA (i.e. CRISPR/Cas locus), as well as carbohydrate fermentation. The 41 strains of P. acidilactici can metabolize a variety of carbon sources, which enhances the adaptability of this species and survival in different environments. This study evaluated the antibacterial ability, genome evolution, and ecological flexibility of P. acidilactici from the perspective of genetics and provides strong supporting evidence for its industrial development and application.

Nutrigenomics reveals potential genetic underpinning of diverse taste preference of Chinese men.

BACKGROUND: Taste preference varies geographically in China. However, studies on Chinese people's taste preference in different regions of China are limited, and are lack of research on the mechanism of differences in taste preference, especially in genetics. OBJECTIVE: This study aims to investigate the characteristics of taste preference of Chinese men, and estimate whether diverse taste preference in Chinese have genetic underpinning. METHODS: We conducted a questionnaire survey on taste preferences on 1076 males from 10 regions of China, and collected another 1427 males from the same regions which genotyped by microarray. We compared the correlation between different taste preference, and evaluated the correlation between the mutation frequency of inhouse database and different taste preference. The putative taste-preference-related genes were further utilized to estimate the candidate relationship on gene and gene network in different taste preference. RESULTS: There was a correlation between different taste preferences in Chinese men. We found 31 SNPs associated with 6 kind of taste preferences. These SNPs located within or nearby 36 genes, and the tastes associated with 4 of these genes (TRPV1, AGT, ASIC2 and GLP1R) are consistent with the previous studies. Moreover, in different tastes which were suggested to be associated with each other, some putative related genes were the same or in the same gene network, such as pathways related with blood pressure, response to stimulus and nervous system. CONCLUSIONS: This study indicates that the diverse taste preference of Chinese men may have genetic underpinning.

Millet-based supplement restored gut microbial diversity of acute malnourished pigs.

The tight association between malnutrition and gut microbiota (GM) dysbiosis enables microbiota-targeting intervention to be a promising strategy. Thus, we used a malnourished pig model to investigate the host response and GM alterations under different diet supplementation strategies. Pigs at age of 4 weeks were fed with pure maize diet to induce malnutrition symptoms, and followed by continuous feeding with maize (Maize, n = 8) or re-feeding using either corn-soy-blend (CSB+, n = 10) or millet-soy-blend based (MSB+, n = 10) supplementary food for 3 weeks. Meanwhile, 8 pigs were fed on a standard formulated ration as control (Ref). The effect of nutritional supplementation was assessed by the growth status, blood chemistry, gastrointestinal pathology, mucosal microbiota composition and colon production of short-chain fatty acids. Compared with purely maize-fed pigs, both CSB+ and MSB+ elevated the concentrations of total protein and globulin in blood. These pigs still showed most malnutrition symptoms after the food intervention period. MSB+ had superior influence on the GM development, exhibiting better performance in both structural and functional aspects. MSB+ pigs were colonized by less Proteobacteria but more Bacteroidetes, Firmicutes and Lachnospira spp. Pearson's correlation analysis indicated a strong correlation between the abundance of mucosal e.g., Faecalibacterium and Lachnospira spp. and body weight, crown-rump length and total serum protein. In conclusion, the malnutrition symptoms were accompanied by an aberrant GM, and millet-based nutritional supplementation showed promising potentials to restore the reduced GM diversity implicated in pig malnutrition.

High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis.

Maternal obesity has been reported to be related to neurodevelopmental disorders in the offspring. However, the underlying mechanisms and effective interventions remain unclear. This cross-sectional study with 778 children aged 7-14 years in China indicated that maternal obesity is strongly associated with children's lower cognition and sociality. Moreover, it has been demonstrated that maternal obesity in mice disrupted the behavior and gut microbiome in offspring, both of which were restored by a high-fiber diet in either dams or offspring via alleviating synaptic impairments and microglial maturation defects. Co-housing and feces microbiota transplantation experiments revealed a causal relationship between microbiota and behavioral changes. Moreover, treatment with the microbiota-derived short-chain fatty acids also alleviated the behavioral deficits in the offspring of obese dams. Together, our study indicated that the microbiota-metabolites-brain axis may underlie maternal obesity-induced cognitive and social dysfunctions and that high dietary fiber intake could be a promising intervention.

Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population.

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10-8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population.

Major genomic regions responsible for wheat yield and its components as revealed by meta-QTL and genotype-phenotype association analyses.

MAIN CONCLUSION: Meta-QTL (MQTL) analysis was done for yield-related traits in wheat. Candidate genes were identified within the refined MQTL and further validated by genotype-phenotype association analysis. Extensive studies have been undertaken on quantitative trait locus/loci (QTL) for wheat yield and its component traits. This study conducted a meta-analysis of 381 QTL related to wheat yield under various environments, including irrigated, drought- and/or heat-stressed conditions. Markers flanking meta-QTL (MQTL) were mapped on the wheat reference genome for their physical positions. Putative candidate genes were examined for MQTL with a physical interval of less than 20 Mbp. A total of 86 MQTL were identified as responsible for yield, of which 34 were for irrigated environments, 39 for drought-stressed environments, 36 for heat-stressed environments, and 23 for both drought- and heat-stressed environments. The high-confidence genes within the physical positions of the MQTL flanking markers were screened in the reference genome RefSeq V1.0, which identified 210 putative candidate genes. The phenotypic data for 14 contrasting genotypes with either high or low yield performance-according to the Australian National Variety Trials-were associated with their genotypic data obtained through ddRAD sequencing, which validated 18 genes or gene clusters associated with MQTL that had important roles for wheat yield. The detected and refined MQTL and candidate genes will be useful for marker-assisted selection of high yield in wheat breeding.

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment.

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.