1.全基因组关联研究剖析了大豆农艺性状的遗传网络
Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean
Genome Biology201718:161
Abstract
Background
Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding.
Results
To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits.
Conclusions
This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.
2.陆地植物中的小RNA和微小RNA代谢途径的保守性与差异性
Conservation and divergence of small RNA pathways and microRNAs in land plants
Genome Biology201718:158
Abstract
Background
As key regulators of gene expression in eukaryotes, small RNAs have been characterized in many seed plants, and pathways for their biogenesis, degradation, and action have been defined in model angiosperms. However, both small RNAs themselves and small RNA pathways are not well characterized in other land plants such as lycophytes and ferns, preventing a comprehensive evolutionary perspective on small RNAs in land plants.
Results
Using 25 representatives from major lineages of lycophytes and ferns, most of which lack sequenced genomes, we characterized small RNAs and small RNA pathways in these plants. We identified homologs of DICER-LIKE (DCL), ARGONAUTE (AGO), and other genes involved in small RNA pathways, predicted over 2600 conserved microRNA (miRNA) candidates, and performed phylogenetic analyses on small RNA pathways as well as miRNAs. Pathways underlying miRNA biogenesis, degradation, and activity were established in the common ancestor of land plants, but the 24-nucleotide siRNA pathway that guides DNA methylation is incomplete in sister species of seed plants, especially lycophytes. We show that the functional diversification of key gene families such as DCL and AGO as observed in angiosperms occurred early in land plants followed by parallel expansion of the AGO family in ferns and angiosperms. We uncovered a conserved AGO subfamily absent in angiosperms.
Conclusions
Our phylogenetic analyses of miRNAs in bryophytes, lycophytes, ferns, and angiosperms refine the time-of-origin for conserved miRNA families as well as small RNA machinery in land plants.
3.改变染色质压缩和组蛋白的甲基化程度驱动拟南芥杂种的非加性基因表达
Altered chromatin compaction and histone methylation drive non-additive gene expression in an interspecific Arabidopsis hybrid
Genome Biology201718:157
Abstract
Background
The merging of two diverged genomes can result in hybrid offspring that phenotypically differ greatly from both parents. In plants, interspecific hybridization plays important roles in evolution and speciation. In addition, many agricultural and horticultural species are derived from interspecific hybridization. However, the detailed mechanisms responsible for non-additive phenotypic novelty in hybrids remain elusive.
Results
In an interspecific hybrid between Arabidopsis thaliana and A. lyrata, the vast majority of genes that become upregulated or downregulated relative to the parents originate from A. thaliana. Among all differentially expressed A. thaliana genes, the majority is downregulated in the hybrid. To understand why parental origin affects gene expression in this system, we compare chromatin packing patterns and epigenomic landscapes in the hybrid and parents. We find that the chromatin of A. thaliana, but not that of A. lyrata, becomes more compact in the hybrid. Parental patterns of DNA methylation and H3K27me3 deposition are mostly unaltered in the hybrid, with the exception of higher CHH DNA methylation in transposon-rich regions. However, A. thaliana genes enriched for the H3K27me3 mark are particularly likely to differ in expression between the hybrid and parent.
Conclusions
It has long been suspected that genome-scale properties cause the differential responses of genes from one or the other parent to hybridization. Our work links global chromatin compactness and H3K27me3 histone modification to global differences in gene expression in an interspecific Arabidopsis hybrid.
4. DNA甲基化的稳定遗传允许在缺少遗传变异的情况下获得表观遗传图谱和研究表观遗传模式
Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation
Genome Biology201718:155
Abstract
Background
Differences in DNA methylation can arise as epialleles, which are loci that differ in chromatin state and are inherited over generations. Epialleles offer an additional source of variation that can affect phenotypic diversity beyond changes to nucleotide sequence. Previous research has looked at the rate at which spontaneous epialleles arise but it is currently unknown how they are maintained across generations.
Results
We used two Arabidopsis thaliana mutation accumulation (MA) lines and determined that over 99.998% of the methylated regions in the genome are stably inherited across each generation indicating that spontaneous epialleles are rare. We also developed a novel procedure that determines genotypes for offspring of genetically identical parents using only DNA methylation data. The resulting epigenotype maps are highly accurate and strongly agree with expected allele frequency and crossover number. Using epigenotype maps, we explore the inheritance of methylation states in regions of differential methylation between the parents of genetic crosses. Over half of the regions show methylation levels consistent with cis inheritance, whereas the other half show evidence of trans-chromosomal methylation and demethylation as well as other possibilities.
Conclusions
DNA methylation is stably inherited by offspring and spontaneous epialleles are rare. The epigenotyping procedure that we describe provides an important first step to epigenetic quantitative trait loci mapping in genetically identical individuals.
5.双链RNA结合蛋白RDE-4可以在线虫中提供RNAi期间自主细胞运动
The double-stranded RNA binding protein RDE-4 can act cell autonomously during feeding RNAi in C. elegans
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages 8463–8473
Abstract
Long double-stranded RNA (dsRNA) can silence genes of matching sequence upon ingestion in many invertebrates and is therefore being developed as a pesticide. Such feeding RNA interference (RNAi) is best understood in the worm Caenorhabditis elegans, where the dsRNA-binding protein RDE-4 initiates silencing by recruiting an endonuclease to process long dsRNA into short dsRNA. These short dsRNAs are thought to move between cells because muscle-specific rescue of rde-4 using repetitive transgenes enables silencing in other tissues. Here, we extend this observation using additional promoters, report an inhibitory effect of repetitive transgenes, and discover conditions for cell-autonomous silencing in animals with tissue-specific rescue of rde-4. While expression of rde-4(+) in intestine, hypodermis, or neurons using a repetitive transgene can enable silencing also in unrescued tissues, silencing can be inhibited wihin tissues that express a repetitive transgene. Single-copy transgenes that express rde-4(+) in body-wall muscles or hypodermis, however, enable silencing selectively in the rescued tissue but not in other tissues. These results suggest that silencing by the movement of short dsRNA between cells is not an obligatory feature of feeding RNAi in C. elegans. We speculate that similar control of dsRNA movement could modulate tissue-specific silencing by feeding RNAi in other invertebrates.
6.密码子使用通过影响果蝇细胞中的翻译延伸的速度来调节蛋白质结构和功能
Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages 8484–8492,
Abstract
Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation. In addition, codon usage regulates ribosome movement and stalling on mRNA during translation. Finally, we show that codon usage affects protein structure and function in vitro and in Drosophila cells. Together, these results suggest that the effect of codon usage on translation elongation speed is a conserved mechanism from fungi to animals that can affect protein folding in eukaryotic organisms.
7. FASTmiR：一种基于RNA的传感器，用于小RNA的体外定量和活细胞定位
FASTmiR: an RNA-based sensor for in vitro quantification and live-cell localization of small RNAs
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages e130
Abstract
Small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), play a variety of important regulatory roles in many eukaryotes. Their small size has made it challenging to study them directly in live cells. Here we describe an RNA-based fluorescent sensor for small RNA detection both in vitro and in vivo, adaptable for any small RNA. It utilizes an sxRNA switch for detection of miRNA–mRNA interactions combined with a fluorophore-binding sequence ‘Spinach’, a GFP-like RNA aptamer for which the RNA–fluorophore complex exhibits strong and consistent fluorescence under an excitation wavelength. Two example sensors, FASTmiR171 and FASTmiR122, can rapidly detect and quantify the levels of miR171 and miR122 in vitro. The sensors can determine relative levels of miRNAs in total RNA extracts with sensitivity similar to small RNA sequencing and northern blots. FASTmiR sensors were also used to estimate the copy number range of miRNAs in total RNA extracts. To localize and analyze the spatial distribution of small RNAs in live, single cells, tandem copies of FASTmiR122 were expressed in different cell lines. FASTmiR122 was able to quantitatively detect the differences in miR122 levels in Huh7 and HEK293T cells demonstrating its potential for tracking miRNA expression and localization in vivo.
8.Structure-seq2：全基因组范围内敏感和准确的鉴定体内RNA的结构
Structure-seq2: sensitive and accurate genome-wide profiling of RNA structure in vivo
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages e135,
Abstract
RNA serves many functions in biology such as splicing, temperature sensing, and innate immunity. These functions are often determined by the structure of RNA. There is thus a pressing need to understand RNA structure and how it changes during diverse biological processes both in vivo and genome-wide. Here, we present Structure-seq2, which provides nucleotide-resolution RNA structural information in vivo and genome-wide. This optimized version of our original Structure-seq method increases sensitivity by at least 4-fold and improves data quality by minimizing formation of a deleterious by-product, reducing ligation bias, and improving read coverage. We also present a variation of Structure-seq2 in which a biotinylated nucleotide is incorporated during reverse transcription, which greatly facilitates the protocol by eliminating two PAGE purification steps. We benchmark Structure-seq2 on both mRNA and rRNA structure in rice (Oryza sativa). We demonstrate that Structure-seq2 can lead to new biological insights. Our Structure-seq2 datasets uncover hidden breaks in chloroplast rRNA and identify a previously unreported N1-methyladenosine (m1A) in a nuclear-encoded Oryza sativa rRNA. Overall, Structure-seq2 is a rapid, sensitive, and unbiased method to probe RNA in vivo and genome-wide that facilitates new insights into RNA biology.
9. CompAnnotate：RNA三维结构中碱基配对相互作用的注释的比较方法
CompAnnotate: a comparative approach to annotate base-pairing interactions in RNA 3D structures
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages e136,
Abstract
The analysis of RNA tertiary structure is hindered by the fact that not too many structural data are available and a significant amount of them are in low resolution. Due to the atomic coordinate errors posed by the limitations of low-resolution RNA three-dimensional structures, it becomes a critical challenge to extract key geometric characteristics of RNA, particularly, the interaction of bases. To address this issue, we have devised a comparative method, named CompAnnotate, that utilizes more precise structural information of high-resolution homologs to annotate the base-pairing interactions in the low-resolution structures, by aligning and making comparative geometric assessments. The benchmarking results show that our method can improve the annotations of the existing methods significantly. We have achieved different levels of improvements for various methods and datasets, including an example of significant sensitivity and precision enhancement from 28 to 57% and from 53 to 82%, respectively.
10.COSINE：用于映射三代含错误的长序列方法
COSINE: non-seeding method for mapping long noisy sequences
Nucleic Acids Research, Volume 45, Issue 14, 21 August 2017, Pages e132,
Abstract
Third generation sequencing (TGS) are highly promising technologies but the long and noisy reads from TGS are difficult to align using existing algorithms. Here, we present COSINE, a conceptually new method designed specifically for aligning long reads contaminated by a high level of errors. COSINE computes the context similarity of two stretches of nucleobases given the similarity over distributions of their short k-mers (k = 3–4) along the sequences. The results on simulated and real data show that COSINE achieves high sensitivity and specificity under a wide range of read accuracies. When the error rate is high, COSINE can offer substantial advantages over existing alignment methods.
11.chromVAR：从单细胞表观基因组数据推断相关的转录因子的可接触性
chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data
Nature Methods (2017) doi:10.1038/nmeth.4401
Abstract
Single-cell ATAC-seq (scATAC) yields sparse data that make conventional analysis challenging. We developed chromVAR (http://www.github.com/GreenleafLab/chromVAR), an R package for analyzing sparse chromatin-accessibility data by estimating gain or loss of accessibility within peaks sharing the same motif or annotation while controlling for technical biases. chromVAR enables accurate clustering of scATAC-seq profiles and characterization of known and de novo sequence motifs associated with variation in chromatin accessibility.
12. 在人和小鼠中miRNA和其启动子的整合表达图谱
An integrated expression atlas of miRNAs and their promoters in human and mouse
Nature Biotechnology (2017) doi:10.1038/nbt.3947
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.
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