A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Role of FY in polyadenylation

APA是存在于真核生物中一种重要的基因表达调控机制，其关键步骤是mRNA前体的核苷酸序列的识别，直接决定了成熟mRNA转录本的序列。本项目研究人员全面探讨了FY不同结构域在poly(A)位点使用中的作用，同时阐明FY与AtCPSF30在polyA信号识别过程中的关系。进一步研究发现FY的WD40结构域的突变与PPLPP结构域的缺失对3’UTR区间polyA位点选择和信号使用有着相反的影响。该论文揭示了拟南芥开花因子FY在选择性多聚腺苷化（Alternative PolyAdenylation, APA）过程中的功能，为植物复杂的多聚腺苷化（polyA）信号识别机制提供遗传学证据，完善了植物polyA过程的分子机制，同时为深入理解通过APA调控植物生长发育和植物对环境响应的分子机制奠定基础。A crucial step for mRNA polyadenylation is poly(A) signal recognition by trans-acting factors. The mammalian cleavage and polyadenylation specificity factor (CPSF) complex components CPSF30 and WDR33 recognize the canonical AAUAAA signal for efficient polyadenylation. In Arabidopsis thaliana, the flowering time regulator FY is the homologue of WDR33. However, its role in mRNA polyadenylation is poorly understood. Using poly(A) tag sequencing, we found that over 50% of alternative polyadenylation (APA) events are altered in fy single mutants or double mutants with Atcpsf30, but mutation of the FY WD40-repeat has a stronger effect than deletion of the plant-unique PPLPP domain. fy mutations disrupt AAUAAA or AAUAAA-like poly(A) signal recognition.Notably, A-rich signal usage is suppressed in the WD40-repeat mutation, but promoted in Pro-Pro-Leu-Pro-Pro (PPLPP)-domain deficiency. However, fy mutations do not aggravate the alteration of signal usage in the Atcpsf30 null mutant. Furthermore, the WD40-repeat mutation shows a preference for 3'UTR shortening, but the PPLPP-domain deficiency shows a preference for lengthening. Interestingly, the WD40-repeat mutant exhibits shortened primary roots and late flowering with alteration of APA of related genes.Importantly, the long transcripts of two APA genes affected in fy are related to abiotic stress responses. These results reveal a conserved and specific role of FY in mRNA polyadenylation.This work was supported in part by a grant from the National Key R&D Project of China (2016YFE0108800), a grant from the U.S. NSF (IOS-154173), both to QQL, and grants (2017M620274, 2018T110649) from China Postdoctoral Science Foundation to JL

Predictive modeling of plant messenger RNA polyadenylation sites

BACKGROUND: One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine [poly(A)] tail. The 3'-end poly(A) track protects mRNA from unregulated degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem. RESULTS: Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called poly(A) site sleuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences. CONCLUSION: Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites

A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immune response in vivo. We conclude that FcγRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity

Monocyte subsets involved in the development of systemic lupus erythematosus and rheumatoid arthritis

Abstract AbstractMonocytes are evolutionally conserved innate immune cells that play essential roles for the protection of the host against pathogens and also produce several inflammatory cytokines. Thus, the aberrant functioning of monocytes may affect not only host defense but also the development of inflammatory diseases. Monocytes are a heterogeneous population with phenotypical and functional differences. Most recent studies have shown that monocytes are divided into three subsets, namely classical, intermediate and non-classical subsets, both in humans and mice. Accumulating evidence showed that monocyte activation is associated with the disease progression in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, it remains to be determined how monocytes contribute to the disease process and which subset is involved. In this review, we discuss the pathogenic role of monocyte subsets in SLE and RA on the basis of current studies by ourselves and others to shed light on the suitability of monocyte-targeted therapies in these diseases.</jats:p

Divergence in the Regulation of the Salt Tolerant Response Between Arabidopsis thaliana and Its Halophytic Relative Eutrema salsugineum by mRNA Alternative Polyadenylation

Salt tolerance is an important mechanism by which plants can adapt to a saline environment. To understand the process of salt tolerance, we performed global analyses of mRNA alternative polyadenylation (APA), an important regulatory mechanism during eukaryotic gene expression, in Arabidopsis thaliana and its halophytic relative Eutrema salsugineum with regard to their responses to salt stress. Analyses showed that while APA occurs commonly in both Arabidopsis and Eutrema, Eutrema possesses fewer APA genes than Arabidopsis (47% vs. 54%). However, the proportion of APA genes was significantly increased in Arabidopsis under salt stress but not in Eutrema. This indicated that Arabidopsis is more sensitive to salt stress and that Eutrema exhibits an innate response to such conditions. Both species utilized distal poly(A) sites under salt stress; however, only eight genes were found to overlap when their 3′ untranslated region (UTR) lengthen genes were compared, thus revealing their distinct responses to salt stress. In Arabidopsis, genes that use distal poly(A) sites were enriched in response to salt stress. However, in Eutrema, the use of poly(A) sites was less affected and fewer genes were enriched. The transcripts with upregulated poly(A) sites in Arabidopsis showed enriched pathways in plant hormone signal transduction, starch and sucrose metabolism, and fatty acid elongation; in Eutrema, biosynthetic pathways (stilbenoid, diarylheptanoid, and gingerol) and metabolic pathways (arginine and proline) showed enrichment. APA was associated with 42% and 29% of the differentially expressed genes (DE genes) in Arabidopsis and Eutrema experiencing salt stress, respectively. Salt specific poly(A) sites and salt-inducible APA events were identified in both species; notably, some salt tolerance-related genes and transcription factor genes exhibited differential APA patterns, such as CIPK21 and LEA4-5. Our results suggest that adapted species exhibit more orderly response at the RNA maturation step under salt stress, while more salt-specific poly(A) sites were activated in Arabidopsis to cope with salinity conditions. Collectively, our findings not only highlight the importance of APA in the regulation of gene expression in response to salt stress, but also provide a new perspective on how salt-sensitive and salt-tolerant species perform differently under stress conditions through transcriptome diversity.</jats:p

Phenotypic and Methylome Responses to Salt Stress in Arabidopsis thaliana Natural Accessions

Salt stress threatens plant growth, development and crop yields, and has become a critical global environmental issue. Increasing evidence has suggested that the epigenetic mechanism such as DNA methylation can mediate plant response to salt stress through transcriptional regulation and transposable element (TE) silencing. However, studies exploring genome-wide methylation dynamics under salt stress remain limited, in particular, for studies on multiple genotypes. Here, we adopted four natural accessions of the model species Arabidopsis thaliana and investigated the phenotypic and genome-wide methylation responses to salt stress through whole-genome bisulfite sequencing (WGBS). We found that salt stress significantly changed plant phenotypes, including plant height, rosette diameter, fruit number, and aboveground biomass, and the change in biomass tended to depend on accessions. Methylation analysis revealed that genome-wide methylation patterns depended primarily on accessions, and salt stress caused significant methylation changes in ∼ 0.1% cytosines over the genomes. About 33.5% of these salt-induced differential methylated cytosines (DMCs) were located to transposable elements (TEs). These salt-induced DMCs were mainly hypermethylated and accession-specific. TEs annotated to have DMCs (DMC-TEs) across accessions were found mostly belonged to the superfamily of Gypsy, a type II transposon, indicating a convergent DMC dynamic on TEs across different genetic backgrounds. Moreover, 8.0% of salt-induced DMCs were located in gene bodies and their proximal regulatory regions. These DMCs were also accession-specific, and genes annotated to have DMCs (DMC-genes) appeared to be more accession-specific than DMC-TEs. Intriguingly, both accession-specific DMC-genes and DMC-genes shared by multiple accessions were enriched in similar functions, including methylation, gene silencing, chemical homeostasis, polysaccharide catabolic process, and pathways relating to shifts between vegetative growth and reproduction. These results indicate that, across different genetic backgrounds, methylation changes may have convergent functions in post-transcriptional, physiological, and phenotypic modulation under salt stress. These convergent methylation dynamics across accession may be autonomous from genetic variation or due to convergent genetic changes, which requires further exploration. Our study provides a more comprehensive picture of genome-wide methylation dynamics under salt stress, and highlights the importance of exploring stress response mechanisms from diverse genetic backgrounds.</jats:p