Biology subjects

Xu, S.

Publications and source records attributed to Xu, S..

32 records · Page 2Linked to original sources

bioRxiv2018

The homoeologous genes for the Rec8-like meiotic cohesin in wheat: structure, function, and evolutionary implication

The Rec8-like cohesin is a cohesion protein essential for orderly chromosome segregation in meiosis. Here, we cloned two Rec8-like homoeologous genes (homoeoalleles) from tetraploid wheat (TtRec8-A1 and TtRec8-B1) and one from hexaploid wheat (TaRec8-D1), and performed expression and functional analyses of the homoeoalleles. Also, we identified other two Rec8 homoeoalleles in hexaploid wheat (TaRec8-A1 and TaRec8-B1) and the one in Aegilops tauschii (AetRec8-D1) by comparative analysis. The coding DNA sequences (CDS) of these six Rec8 homoeoalleles are all 1,827 bp in length, encoding 608 amino acids. They differed from each other primarily in introns although single nucleotide polymorphisms were detected in CDS. Substantial difference was observed between the homoeoalleles from the subgenome B (TtRec8-B1 and TaRec8-B1) and those from the subgenomes A and D (TtRec8-A1, TaRec8-A1, and TaRec8-D1). TtRec8-A1 expressed dominantly over TtRec8-B1, but comparably to TaRec8-D1. Therefore, the Rec8 homoeoalleles from the subgenomes A and D may be functionally more active than the one from the subgenome B in wheat. The structural variation and differential expression of the Rec8 homoeoalleles indicate a unique cross-genome coordination of the homoeologous genes in the polyploid, and imply the distinction of the wheat subgenome B from other subgenomes in the origin and evolution.\n\nHIGHLIGHTThis work revealed the structural and expression patterns of the Rec8-like homoeologous genes in polyploid wheat, implying a unique origin and evolutionary route of the wheat B subgenome.

genetics↗

bioRxiv2018

Systematic differences between visually-relevant global and local image statistics of brain MRI and natural scenes

An important heuristic in developing image processing technologies is to mimic the computational strategies used by humans. Relevant to this, recent studies have shown that the human brains processing strategy is closely matched to the characteristics of natural scenes, both in terms of global and local image statistics. However, structural MRI images and natural scenes have fundamental differences: the former are two-dimensional sections through a volume, the latter are projections. MRI image formation is also radically different from natural image formation, involving acquisition in Fourier space, followed by several filtering and processing steps that all have the potential to alter image statistics. As a consequence, aspects of the human visual system that are finely-tuned to processing natural scenes may not be equally well-suited for MRI images, and identification of the differences between MRI images and natural scenes may lead to improved machine analysis of MRI.\n\nWith these considerations in mind, we analyzed spectra and local image statistics of MRI images in several databases including T1 and FLAIR sequence types and of simulated MRI images,[1]-[6] and compared this analysis to a parallel analysis of natural images[7] and visual sensitivity[7][8]. We found substantial differences between the statistical features of MRI images and natural images. Power spectra of MRI images had a steeper slope than that of natural images, indicating a lack of scale invariance. Independent of this, local image statistics of MRI and natural images differed: compared to natural images, MRI images had smaller variations in their local two-point statistics and larger variations in their local three-point statistics - to which the human visual system is relatively insensitive. Our findings were consistent across MRI databases and simulated MRI images, suggesting that they result from brain geometry at the scale of MRI resolution, rather than characteristics of specific imaging and reconstruction methods.

neuroscience↗

bioRxiv2018

A compromised gsdf signaling leads to gamatogenesis confusion and subfertility in medaka

Summary statementGsdf signals trigger the gamatogenesis, alter the somatic expression of Fsh/Lh receptors and brain type aromatase in medaka brain and gonad.\n\nAbstractGonadal soma-derived factor (gsdf) and anti-Mullerian hormone (amh) are somatic male determinants in several species of teleosts, although the mechanisms by which they trigger the indifferent germ cells into the male pathway remain unknown. This study aimed to decipher the roles of gsdf/amh in directing the sexual fate of germ cells using medaka as a model. Transgenic lines (TgcryG) that restrictively and persistently express a Gsdf-Gfp fusion protein in the lens and the hypothalamus-pituitary-gonad (HPG) axis, were generated under the control of a mouse {gamma}F-crystallin promoter. A high frequency (44.4%) of XX male sex reversals was obtained in TgcryG lines, indicating that signals of gsdf-expressing cells in HPG were enough for the spermatogenesis activation in the genetic females. Furthermore, all TgcryG XY individuals with endogenous gsdf depletion (named Sissy) displayed intersex (100%) with enlarged ovotestis in contrast to a giant ovary developed in XY gsdf deficiency. The heterogeneous expression of gsdf led to the confusion of gamatogenesis and ovotestis development, similar to some hotei (amhr2) mutants, suggests that the signaling balance of gsdf/amh is essential for proper gamatogenesis, maintaining sex steroid production and gonadotropin secretion, which are evolutionarily conserved across phyla.

evolutionary biology↗

bioRxiv2017

In vivo multiphoton fluorescence imaging with polymer dots

Deep in vivo imaging of vasculature requires small, bright, and photostable fluorophores suitable for multiphoton microscopy (MPM). Although semiconducting polymer dots (pdots) are an emerging class of highly fluorescent contrast agents with favorable advantages for the next generation of in vivo imaging, their use for deep multiphoton imaging has never before been demonstrated. Here we characterize the multiphoton properties of three pdot variants (CNPPV, PFBT, and PFPV) and demonstrate deep imaging of cortical microvasculature in C57 mice. Specifically, we measure the two-versus three-photon power dependence of these pdots and observe a clear three-photon excitation signature at wavelengths longer than 1300 nm, and a transition from two-photon to three-photon excitation within a 1060 - 1300 nm excitation range. Furthermore, we show that pdots enable in vivo two-photon imaging of cerebrovascular architecture in mice up to 850 m beneath the pial surface using 800 nm excitation. In contrast with traditional multiphoton probes, we also demonstrate that the broad multiphoton absorption spectrum of pdots permits imaging at longer wavelengths ({lambda}ex = 1,060 and 1225 nm). These wavelengths approach an ideal biological imaging wavelength near 1,300 nm and confer compatibility with a high-power ytterbium-fiber laser and a high pulse energy optical parametric amplifier, resulting in substantial improvements in signal-to-background ratio (>3.5-fold) and greater cortical imaging depths of 900 m and 1300 m. Ultimately, pdots are a versatile tool for MPM due to their extraordinary brightness and broad absorption, which will undoubtedly unlock the ability to interrogate deep structures in vivo.

bioengineering↗

bioRxiv2017

Identification of genetic factors controlling domestication-related traits in cowpea (Vigna unguiculata L. Walp)

Cowpea (Vigna unguiculata L. Walp) is a warm-season legume with a genetically diverse gene-pool composed of wild and cultivated forms. Cowpea domestication involved considerable phenotypic changes from the wild progenitor, including reduction of pod shattering, increased organ size, and changes in flowering time. Little is known about the genetic basis underlying these changes. In this study, 215 recombinant inbred lines derived from a cross between a cultivated and a wild cowpea accession were used to evaluate nine domestication-related traits (pod shattering, peduncle length, flower color, flowering time, 100-seed weight, pod length, leaf length, leaf width and seed number per pod). A high-density genetic map containing 17,739 single nucleotide polymorphisms was constructed and used to identify 16 quantitative trait loci (QTL) for these nine domestication-related traits. Candidate genes underlying each of those 16 QTL were identified. Four regions with clusters of QTL were identified, including one on chromosome 8 related to increased organ size. This study provides new knowledge of the genomic regions controlling domestication-related traits in cowpea as well as candidate genes underlying those QTL. This information can help to exploit wild relatives in cowpea breeding programs.\n\nKey messageThis study identified regions of the cowpea genome that played an important role in cowpea domestication, including a hotspot region for increased organ size

genetics↗

bioRxiv2017

Genome-wide homology analysis reveals new insights into the origin of the wheat B genome

Wheat is a typical allopolyploid with three homoeologous subgenomes (A, B, and D). The ancestors of the subgenomes A and D had been identified, but not for the subgenome B. The goatgrass Aegilops speltoides (genome SS) has been controversially considered a candidate for the ancestor of the wheat B genome. However, the relationship of the Ae. speltoides S genome with the wheat B genome remains largely obscure, which has puzzled the wheat research community for nearly a century. In the present study, the genome-wide homology analysis identified perceptible homology between wheat chromosome 1B and Ae. speltoides chromosome 1S, but not between other chromosomes in the B and S genomes. An Ae. speltoides-originated segment spanning a genomic region of approximately 10.46 Mb was identified on the long arm of wheat chromosome 1B (1BL). The Ae. speltoides-originated segment on 1BL was found to co-evolve with the rest of the B genome in wheat species. Thereby, we conclude that Ae. speltoides had been involved in the origin of the wheat B genome, but should not be considered an exclusive ancestor of this genome. The wheat B genome might have a polyphyletic origin with multiple ancestors involved, including Ae. speltoides. These novel findings provide significant insights into the origin and evolution of the wheat B genome, and will facilitate polyploid genome studies in wheat and other plants as well.

genetics↗

bioRxiv2017

Genome-wide Variants of Eurasian Facial Shape Differentiation and a prospective model of DNA based Face Prediction

It is a long standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association analyses were conducted on a discovery panel of Uyghurs. Six significant loci were identified four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals, and tested in hypothetic forensic scenarios.

genetics↗

bioRxiv2017

Semi-Parametric Covariate-Modulated Local False Discovery Rate For Genome-Wide Association Studies

While genome-wide association studies (GWAS) have discovered thousands of risk loci for heritable disorders, so far even very large meta-analyses have recovered only a fraction of the heritability of most complex traits. Recent work utilizing variance components models has demonstrated that a larger fraction of the heritability of complex phenotypes is captured by the additive effects of SNPs than is evident only in loci surpassing genome-wide significance thresholds, typically set at a Bonferroni-inspired p [≤] 5 x 10-8. Procedures that control false discovery rate can be more powerful, yet these are still under-powered to detect the majority of non-null effects from GWAS. The current work proposes a novel Bayesian semi-parametric two-group mixture model and develops a Markov Chain Monte Carlo (MCMC) algorithm for a covariate-modulated local false discovery rate (cmfdr). The probability of being non-null depends on a set of covariates via a logistic function, and the non-null distribution is approximated as a linear combination of B-spline densities, where the weight of each B-spline density depends on a multinomial function of the covariates. The proposed methods were motivated by work on a large meta-analysis of schizophrenia GWAS performed by the Psychiatric Genetics Consortium (PGC). We show that the new cmfdr model fits the PGC schizophrenia GWAS test statistics well, performing better than our previously proposed parametric gamma model for estimating the non-null density and substantially improving power over usual fdr. Using loci declared significant at cmfdr [≤] 0.20, we perform follow-up pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) homo sapiens pathways database. We demonstrate that the increased yield from the cmfdr model results in an improved ability to test for pathways associated with schizophrenia compared to using those SNPs selected according to usual fdr.

bioinformatics↗

bioRxiv2017

Prodomain-Growth Factor Swapping in the Structure of pro-TGF-β1

Transforming growth factor (TGF)-{beta} is synthesized as a proprotein that dimerizes in the endoplasmic reticulum. After processing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain in each monomer, pro-TGF-{beta} is secreted and stored in latent complexes. It is unclear which prodomain and GF monomer are linked prior to proprotein convertase (PC) cleavage, and how much conformational change occurs following cleavage. We have determined a structure of pro-TGF-{beta}1 with the PC cleavage site mutated, to mimic the structure of the TGF-{beta}1 proprotein. Our structure demonstrates that the prodomain arm domain in one monomer is linked to the GF that interacts with the arm domain in the other monomer in the dimeric structure, i.e., the prodomain arm domain and GF domain in each monomer are swapped. Swapping has important implications for the mechanism of biosynthesis in the TGF-{beta} family and is relevant to the mechanism for preferential formation of heterodimers over homodimers for some members of the TGF-{beta} family. Our structure also provides comparisons between independent TGF-{beta}1 crystal structures and between human and porcine pro-TGF-{beta}1.

biochemistry↗

bioRxiv2017

Intrinsic Hippocampal-Caudate Interaction Correlates with Human Navigation

It has been indicated that both egocentric and allocentric representation systems exist in parallel, and combine to support spatial navigation according to the task. Identifying the neuronal mechanisms and functional roles of the interactions between the two systems promises to provide new insights into the organization of human navigation network. Here we combined resting-state fMRI and behavioral tasks to investigate how the core structures of these systems (i.e., hippocampus and caudate) functionally interact, and further examined their behavioral relevance in navigation in healthy young adults (N = 190). We found a slightly positive connectivity between the hippocampus and caudate (especially in good navigators), suggesting an effective hippocampal-caudate cross talk, which may facilitate the functional integration of the two systems. Interestingly, the hippocampal-caudate interaction correlated with better self-reported navigation ability. Moreover, using an extra 3D pointing task in virtual reality, we found that individuals behavioral performance could be largely predicted by the hippocampal-caudate interactions. Overall, our study demonstrated the intrinsic interaction between two representation systems of the navigation network and its functional roles in behaviors, and further study on dynamic interaction would help us understand better their role in normal aging and psychiatric disorders.

neuroscience↗

bioRxiv2017

The rapid evolution of alternative splicing in plants

Alternative pre-mRNA splicing (AS) is prevalent among all plants and is involved in many interactions with environmental stresses. However, the evolutionary patterns and underlying mechanisms of AS in plants remain unclear. By analyzing the transcriptomes of six plant species, we revealed that AS diverged rapidly among closely related species, largely due to the gains and losses of AS events among orthologous genes. Furthermore, AS that generates transcripts containing premature termination codons (PTC), although only representing a small fraction of the total AS, are more conserved than those that generate non-PTC containing transcripts, suggesting that AS coupled with nonsense-mediated decay (NMD) might play an important role in regulating mRNA levels post-transcriptionally. With a machine learning approach we analyzed the key determinants of AS to understand the mechanisms underlying its rapid divergence. Among the studied species, the presence/absence of alternative splicing site (SS) within the junction, the distance between the authentic SS and the nearest alternative SS, the size of exon-exon junctions were the major determinants for both alternative 5 donor site and 3acceptor site, suggesting a relatively conserved AS mechanism. Comparative analysis further demonstrated that variations of the identified AS determinants, mostly are located in introns, significantly contributed to the AS turnover among closely related species in both Solanaceae and Brassicaceae taxa. These new mechanistic insights into the evolution of AS in plants highlight the importance of post-transcriptional regulation in mediating plant-environment interactions.\n\nOne sentence summaryChanges of intron located splicing regulators contributed to the rapid evolution of alternative splicing in plants.

plant biology↗

bioRxiv2017

Wild tobacco genomes reveal the evolution of nicotine biosynthesis

Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and N. obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinic acid dinucleotide (NAD) pathways. While the duplication of the former is shared among several Solanaceous genera which produce polyamine-derived tropane alkaloids, the innovation and efficient production of nicotine in the genus Nicotiana required lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor (ERF) that activates the expression of all nicotine biosynthetic genes. Furthermore, TE insertions that incorporated transcription factor binding motifs also likely contributed to the coordinated metabolic flux of the nicotine biosynthetic pathway. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.

genomics↗

bioRxiv2016

Inference of Multiple-wave Admixtures by Length Distribution of Ancestral Tracks

The ancestral tracks in admixed genomes are of valuable information for population history inference. A few methods have been developed to infer admixture history based on ancestral tracks. Nonetheless, these methods suffered the same flaw that only population admixture history under some specific models can be inferred. In addition, the inference of history might be biased or even unreliable if the specific model is deviated from the real situation. To address this problem, we firstly proposed a general discrete admixture model to describe the admixture history with multiple ancestral populations and multiple-wave admixtures. We next deduced the length distribution of ancestral tracks under the general discrete admixture model. We further developed a new method, MultiWaver, to explore the multiple-wave admixture histories. Our method could automatically determine an optimal admixture model based on the length distribution of ancestral tracks, and estimate the corresponding parameters under this optimal model. Specifically, we used a likelihood ratio test (LRT) to determine the number of admixture waves, and implemented an expectation??maximization (EM) algorithm to estimate parameters. We used simulation studies to validate the reliability and effectiveness of our method. Finally, good performance was observed when our method was applied to real datasets of African Americans, Mexicans, Uyghurs, and Hazaras.

genetics↗

bioRxiv2016

Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with polynomial functions

To infer the histories of population admixture, one important challenge with methods based on the admixture linkage disequilibrium (ALD) is to get rid of the effect of source LD (SLD) which is directly inherited from source populations. In previous methods, only the decay curve of weighted LD between pairs of sites whose genetic distance were larger than a certain starting distance was fitted by single or multiple exponential functions, for the inference of recent single- or multiple-wave of admixture. However, the effect of SLD has not been well defined and no tool has been developed to estimate the effect of SLD on weighted LD decay. In this study, we defined the SLD in the formularized weighted LD statistic under the two-way admixture model, and proposed polynomial spectrum (p-spectrum) to study the weighted SLD and weighted LD. We also found reference populations could be used to reduce the SLD in weighted LD statistic. We further developed a method, iMAAPs, to infer Multiple-wave Admixture by fitting ALD using Polynomial spectrum. We evaluated the performance of iMAAPs under various admixture models in simulated data and applied iMAAPs into analysis of genome-wide single nucleotide polymorphism data from the Human Genome Diversity Project (HGDP) and the HapMap Project. We showed that iMAAPs is a considerable improvement over other current methods and further facilitates the inference of the histories of complex population admixtures.

evolutionary biology↗