Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI) project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1) were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of Pac Bio,10? Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of597 participants and identified 24.85 million(M) single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677 T),we hypothesize that there exists a ‘‘comfort" zone for a high frequency of 677 T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.     

Genome size of 14 species of fireflies (Insecta,Coleoptera, Lampyridae)

Eukaryotic genome size data are important both as the basis for comparative research into genome evolution and as estimators of the cost and difficulty of genome sequencing programs for non-model organisms.In this study,the genome size of 14 species of fireflies (Lampyridae) (two genera in Lampyrinae,three genera in Luciolinae,and one genus in subfamily incertae sedis) were estimated by propidium iodide (PI)-based flow cytometry.The haploid genome sizes of Lampyridae ranged from 0.42 to 1.31 pg,a 3.1-fold span.Genome sizes of the fireflies varied within the tested subfamilies and genera.Lamprigera and Pyrocoelia species had large and small genome sizes,respectively.No correlation was found between genome size and morphological traits such as body length,body width,eye width,and antennal length.Our data provide additional information on genome size estimation of the firefly family Lampyridae.Furthermore,this study will help clarify the cost and difficulty of genome sequencing programs for non-model organisms and will help promote studies on firefly genome evolution.     

The effects of fresh and rapid desiccated tissue on estimates of Ophiopogoneae genome size

Fresh plant material is usually used for genome size estimation by flow cytometry(FCM). Lack of fresh material is cited as one of the main reasons for the dearth of studies on plants from remote locations.Genome sizes in fresh versus desiccated tissue of 16 Ophiopogoneae species and five model plant species were estimated. Our results indicated that desiccated tissue was suitable for genome size estimation; this method enables broader geographic sampling of plants when fresh tissue collection is not feasible. To be useful, after dessication the Ophiopogoneae sample should be green without brown or yellow markings;it should be stored in deep freezer at à80C, and the storage time should be no more than 6 months.     

Identification and characterization of genes involved in the jasmonate biosynthetic and signaling pathways in mulberry （Morus notabilis）

Jasmonate （JA） is an important phytohormone regulating growth, development, and environmental response in plants, particularly defense response against herbivorous insects. Recently, completion of the draft genome of the mulberry （Morus notabilis） in conjunction with genome sequencing of silkworm （Bombyx mori） provides an opportuni-ty to study this unique plant-herbivore interaction. Here, we identified genes involved in JA biosynthetic and signaling pathways in the genome of mulberry for the first time, with the majority of samples showing a tissue-biased expression pattern. The analysis of the representative genes 12-oxophy-todienoic acid reductase （OPRs） and jasmonate ZIM-domain （JAZs） was performed and the results indicated that the mulberry genome contains a relatively smal number of JA biosynthetic and signaling pathway genes. A gene encoding an＆amp;nbsp;important repressor, MnNINJA, was identified as an alternative splicing variant lacking an ethylene-responsive element binding factor-associated amphiphilic repression motif. Having this fundamental information wil facilitate future functional study of JA-related genes pertaining to mulberry-silkworm interactions.     

Bacterial Phosphoproteomic Analysis Reveals the Correlation Between Protein Phosphorylation and Bacterial Pathogenicity

Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria. This review focuses on the implications of bacterial phosphoproteome in bacterial pathogenicity and highlights recent development of methods in phosphoproteomics and the connectivity of the phosphorylation networks. Recent technical developments in the high accuracy mass spectrometry have dramatically transformed proteomics and made it possible the characterization of a few exhaus- tive site-specific bacterial phosphoproteomes. The high abundance of tyrosine phosphorylations in a few bacterial phosphoproteomes suggests their roles in the pathogenicity, especially in the case of pathogen-host interactions; the high abundance of multi-phosphorylation sites in bacterial phosphoprotein is a compensation of the relatively small phosphorylation size and an indicator of the delicate regulation of protein functions.     

The magic of four： induction of pluripotent stem cells from somatic cells by Oct4, Sox2, Myc and Klf4

The developmental process from a fertilized egg to agrown adult is programmed with remarkable accuracy.While the genetic information of the fertilized egg and itsdescendent somatic cells are the same, it is the selectiveexpressions of the same genome that give rise to the 200or so different cell types in an adult. The differentiatedstates of these adult cells are maintained epigenetically,presumably through the modification of chromatins and theassociated histones. In higher mammals, it was thought thatthe differentiation process is irreversible until the successfulcloning of Dolly [1]. By transferring a nucleus from a fullydifferentiated cell in the mammary gland, Wilmut and col-leagues were able to generate an exact replica of a highermammal, the Doily [1]. This work not only demonstratedthat the genome of differentiated cells can be reprogrammedinto an embryonic state and then to resume a full-fledgeddevelopmental process to generate a normal adult, but alsorejuvenated the field of animal cloning. The prospect thata somatic cell from a patient may be reprogrammed to the     

Isolation and characterization of glacier VMY22, a novel lytic cold-active bacteriophage of Bacillus cereus

As a unique ecological system with low temperature and low nutrient levels, glaciers are considered a "living fossil" for the research of evolution. In this work, a lytic cold-active bacteriophage designated VMY22 against Bacillus cereus MYB41-22 was isolated from Mingyong Glacier in China, and its characteristics were studied. Electron microscopy revealed that VMY22 has an icosahedral head(59.2 nm in length, 31.9 nm in width) and a tail(43.2 nm in length). Bacteriophage VMY22 was classified as a Podoviridae with an approximate genome size of 18 to 20 kb. A one-step growth curve revealed that the latent and the burst periods were 70 and 70 min, respectively, with an average burst size of 78 bacteriophage particles per infected cell. The pH and thermal stability of bacteriophage VMY22 were also investigated. The maximum stability of the bacteriophage was observed to be at pH 8.0 and it was comparatively stable at p H 5.0–9.0. As VMY22 is a cold-active bacteriophage with low production temperature, its characterization and the relationship between MYB41-22 and Bacillus cereus bacteriophage deserve further study.     

Retromer Subunits VPS35A and VPS29 Mediate Prevacuolar Compartment （PVC） Function in Arabidopsis

Intracellular protein routing is mediated by vesicular transport which is tightly regulated in eukaryotes. The protein and lipid homeostasis depends on coordinated delivery of de novo synthesized or recycled cargoes to the plasma membrane by exocytosis and their subsequent removal by rerouting them for recycling or degradation. Here, we report the characterization of protein affected trafficking 3 （pat3） mutant that we identified by an epifluorescence-based for- ward genetic screen for mutants defective in subcellular distribution of Arabidopsis auxin transporter PIN1-GFR While pat3 displays largely normal plant morphology and development in nutrient-rich conditions, it shows strong ectopic intracellular accumulations of different plasma membrane cargoes in structures that resemble prevacuolar compart- ments （PVC） with an aberrant morphology. Genetic mapping revealed that pat3 is defective in vacuolar protein sorting 35A （VPS35A）, a putative subunit of the retromer complex that mediates retrograde trafficking between the PVC and trans-Golgi network. Similarly, a mutant defective in another retromer subunit, vps29, shows comparable subcellular defects in PVC morphology and protein accumulation. Thus, our data provide evidence that the retromer components VPS35A and VPS29 are essential for normal PVC morphology and normal trafficking of plasma membrane proteins in plants. In addition, we show that, out of the three VPS35 retromer subunits present in Arabidopsis thaliana genome, the VPS35 homolog A plays a prevailing role in trafficking to the lyric vacuole, presenting another level of complexity in the retromer-dependent vacuolar sorting.     

Leaf hydraulics coordinated with leaf economics and leaf size in mangrove species along a salinity gradientOA

Independence among leaf economics,leaf hydraulics and leaf size confers plants great capability in adapting to heterogeneous environments.However,it remains unclear whether the independence of the leaf traits revealed across species still holds within species,especially under stressed conditions.Here,a suite of traits in these dimensions were measured in leaves and roots of a typical mangrove species,Ceriops tagal,which grows in habitats with a similar sunny and hot environment but different soi...     

Small RNA in rice genome

Rice has many characteristics of a model plant. The recent completion of the draft of the rice genome represents an important advance in our knowledge of plant biology and also has an important contribution to the understanding of general genomic evolution. Besides the rice genome finishing map, the next urgent step for rice researchers is to annotate the genes and non-coding functional sequences. The recent work shows that noncoding RNAs (ncRNAs) play significant roles in biological systems. We have explored all the known small RNAs (a kind of ncRNA) within rice genome and other six species sequences, including Arabidopsis, maize, yeast, worm, mouse and pig. As a result we find 160 out of 552 small RNAs (sRNAs) in database have ho-mologs in 108 rice scaffolds, and almost all of them (99.41 %) locate in intron regions of rice by gene predication. 19 sRNAs only appear in rice. More importantly, we find two special U14 sRNAs: one is located in a set of sRNA ZMU14SNR9(s) which only appears in three plants,     

Tissue-specific temporal exome capture revealed muscle-specific genes and SNPs in Indian buffalo (Bubalus bubalis)

Whole genome sequencing of buffalo is yet to be completed,and in the near future it may not be possible to identify an exome(coding region of genome) through bioinformatics for designing probes to capture it.In the present study,we employed in solution hybridization to sequence tissue specific temporal exomes(TST exome) in buffalo.We utilized cDNA prepared from buffalo muscle tissue as a probe to capture TST exomes from the buffalo genome.This resulted in a prominent reduction of repeat sequences(up to 40%) and an enrichment of coding sequences(up to 60%).Enriched targets were sequenced on a 454 pyro-sequencing platform,generating 101,244 reads containing 24,127,779 high quality bases.The data revealed 40,100 variations,of which 403 were indels and 39,218 SNPs containing 195 nonsynonymous candidate SNPs in protein-coding regions.The study has indicated that 80% of the total genes identified from capture data were expressed in muscle tissue.The present study is the first of its kind to sequence TST exomes captured by use of cDNA molecules for SNPs found in the coding region without any prior sequence information of targeted molecules.     

Does sexual dimorphism vary by population? Laryngeal and ear anatomy in cricket frogs

Acoustic communication in many anuran species can show the effects of both natural and sexual selection. This is reflected in the sexually dimorphic an atomy of the lary nx and ear structures, as well as the allometric relationship of these morphological traits to head or body size. In this study, we examined laryngeal and ear structures of cricket frogs Acris crepitans not only as sexually dimorphic characteristics, but also as they differ across populations in environmentally different habitats. We used 2-way ANOVA to determine whether the volumetric or linear measurements of these structures differed by sex and population. Females have significantly larger body, head, and ear sizes, but significantly smaller larynges than males. Furthermore, females as well as males show larger body and head sizes, ears, and larynges in a dryer open habitat. An ANCOVA analysis shows that males, but not females, differ in laryngeal size across populations beyond the allometric changes attributable to head size alone indicating that males have a greater degree of laryngeal population variation. In contrast, our covariate analysis found that in both sexes many of the ear differences are non-sigrdficant once head size is accounted for, suggesting that most of the population-level ear variation is due to allometric effects of body size. We conclude that although both sexes show size differences in the larynx related to selection for larger body size in dry, open habitats, selection on males for larger larynx size related to the production of lower frequency calls in those habitats does not result in correlated changes in the female larynx. The results suggest that in anurans, selection for changes in body and head size affects both sexes equally, male calls and the vocal structures responsible for them can further diversify without concordant changes in females.     

Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer's Disease

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases, such as prion diseases and Alzheimer's disease(AD). Like prion diseases, AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential. Although it remains elusive how protein aggregation leads to AD, it is becoming clear that cellular prion protein(PrP~C ) plays an important role in AD pathogenesis. Here, we briefly reviewed AD pathogenesis and focused on recent progresses how PrP~C contributed to AD development. In addition, we proposed a potential mechanism to explain why infectious agents, such as viruses, conduce AD pathogenesis. Microbe infections cause Aβ deposition and upregulation of PrP~C , which lead to high affinity binding between Aβ oligomers and PrP~C . The interaction between PrP~C and Aβ oligomers in turn activates the Fyn signaling cascade, resulting in neuron death in the central nervous system(CNS). Thus, silencing PrP~C expression may turn out be an effective treatment for PrP~C dependent AD.     

Morphological characteristics of leaf epidermis and size variation of leaf,flower and fruit in different ploidy levels in Buddleja macrostachya （Buddlejaceae）

Buddleja macrostachya （Buddlejaceae） is a widespread shrub native to the Sino-Himalayan mountains and beyond. It has been found to occur at two ploidy levels, hexaploid, 2n=6x=114 and dodecaploid, 2n= 12x=228. To determine if morphological characters might be used as indicators of ploidy levels, we measured floral and fruit length, relative and absolute leaf size, trichome density on both leaf surfaces, and stomatal density and length in different populations orB. macrostachya. In general, flower and fruit length, absolute leaf size, and stomatal length in,eased with an increase at ploidy level （P〈0.01）, whereas adaxial cell and stomatal density decreased with an increase at ploidy level （P〈0.01）. We found no conspicuous differences in relative leaf size （P〉0.05） in different populations. Other characters studied such as trichome type, cuticular membrane and ornamentation of stomata, cell and stomatal shape, and anticlinal wall pattern were quite constant in this species. Thus it appears that flower and fruit length, absolute leaf size, and stomatal frequency and length can be used to distinguish hexaptoid from dodecaploid cytotypes either in the field or in herbarium specimens.     

The structure analysis and antigenicity study of the N protein of SARS-CoV

The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with o     

Genomic and mitochondrial evidence of ancient isolations and extreme introgression in the four-lined snake

Comparing mitochondrial and genomic phylogenies is an essential tool for investigating speciation processes,because each genome carries different inheritance properties and evolutionary characteristics.Furthermore,mitonuclear discordance may arise from ecological adaptation,historic isolation,population size changes,and sex-biased dispersal.Closely related taxa are expected to experience gene flow;however,this may not be true for insular populations or populations isolated in refugia.The four-lined snake Elaphe quatuorlineata has a fragmented distribution,separating populations of the Italian and Balkan Peninsulas,whereas several insular Aegean populations of significantly smaller body size(Cyclades island group and Skyros Island,Greece)are currently considered distinct subspecies.We constructed the species-tree phylogeny of this species utilizing genome-wide single nucleotide polymorphisms and a gene-tree based on complete cytochrome b sequences,aiming to detect convergence and discrepancies between biparentally and maternally inherited genomes.Population structuring,phylogenetic patterns and migration events among geographically defined lineages supported our hypothesis of isolation in multiple sub-refugia.Where biogeographical barriers did not restrict subsequent dispersal,extensive genetic exchange occurred between mainland Balkan populations.This process has led to the mitochondrial sweep of an ancestral mitolineage that survived only in peripheral(East Greece)and insular populations(North Cyclades and Skyros).The Central Cyclades represent an ancient lineage for both molecular markers that emerged almost 3.3 Mya.Considering their distinct morphology,insular E.quatuorlineata populations should be the future focus of an extensive sampling,especially since the mitonuclear discordance observed in this species could be related to ecological adaptations,such as the island-dwarfism phenomenon.