Characterization of PmDGM conferring powdery mildew resistance in Chinese wheat landrace Duanganmang

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease threatening yield and quality. Host resistance is considered the most effective and preferred means to control this disease. Wheat landrace Duanganmang (DGM) showed high resistance or near immunity to Bgt mixture from Henan province, China. DGM was crossed with highly susceptible Chinese wheat landrace Huixianhong (HXH) and cultivar Shimai 15 (SM15) to produce genetic populations. The resistance of DGM to Bgt isolate E09 was shown to be controlled by a single dominant Mendelian factor, tentatively designated PmDGM. Marker analysis and 55K SNP (single nucleotide polymorphism) array scanning showed that this gene was positioned in the Pm5 interval (2.4 cM or 1.61 Mb) flanked by Xhenu099 and Xmp1158 in the Chinese Spring reference genome. Homology-based cloning and sequence analysis demonstrated that DGM has the identical NLR gene (Pm5e) and RXL gene reported in Fuzhuang 30 (FZ30) conferring and modifying the powdery mildew resistance, respectively. However, based on the different reaction patterns to the Bgt isolate B15 between DGM and FZ30, we speculate that DGM may have two tightly linked genes that could not be separated in the current mapping population, one is PmDGM and the other is Pm5e. Hence, this study provides a valuable resistance resource for improvement of powdery mildew resistance.

Complete genomic sequence and analysis of β2 toxin gene mapping of Clostridium perfringens JXJA17 isolated from piglets in China

Clostridium perfringens (Cp) is a ubiquitous opportunistic pathogen of humans and animals in the natural environment and animal intestines. The pathogenicity of Cp depends on the production of toxins encoded by genes on the chromosomes or plasmids. In contemporary literature, there is no clear consensus about the pathogenicity of CpA β2 toxin. To analyze the homology of the genome of piglet source CpA and its β2 toxin, we sequenced the whole genome of strain JXJA17 isolated from diarrhea piglets using the Illumina Miseq and Pacbio Sequel platforms. The genome was composed of a circular chromosome with 3,324,072 bp (G + C content: 28.51%) and nine plasmids. Genome and 16S rDNA homology analysis revealed a close relation of the JXJA17 strain with the JGS1495, Cp-06, Cp-16, and FORC_003 strains. These strains were isolated from different samples and belonged to different toxin-types. JXJA17 strain was found to carry two toxin genes (plc and cpb2). In contrast to other Cp strains, the cpb2 of JXJA17 was located on a large plasmid (58 kb) with no co-localization of other toxin genes or antibiotic resistance genes. Analysis of JXJA17 genome homology and its cpb2 would facilitate our further study the relationship between β2 toxin and piglet diarrhea.

The U94 Gene of Human Herpesvirus 6: A Narrative Review of Its Role and Potential Functions

Human herpesvirus 6 (HHV-6) is a β-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A/B show high genome homology and harbor the conserved U94 gene, which is limited to HHV-6 and absent in all the other human herpesviruses. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation. During natural infection, U94 elicits an immune response, and the prevalence and extent of the anti-U94 response are associated with specific diseases. Notably, U94 can entirely reproduce some virus effects at the cell level, including inhibition of cell migration, induction of cytokines and HLA-G expression, and angiogenesis inhibition, supporting a direct U94 role in the development of HHV-6-associated diseases. Moreover, specific U94 properties, such as the ability to modulate angiogenesis pathways, have been exploited to counteract cancer development. Here, we review the information available on this key HHV-6 gene, highlighting its potential uses.

De-novo Assembly of RaTG13 Genome Reveals Inconsistencies Further Obscuring SARS-CoV-2 Origins

An intense scientific debate is ongoing as to the origin of SARS-CoV-2. An oft-cited piece of information in this debate is the genome sequence of a bat coronavirus strain referred to as RaTG13 1 mentioned in a recent Nature paper 2 showing 96.2% genome homology with SARS-CoV-2. This is discussed as a fossil record of a strain whose current existence is unknown. The said strain is conjectured by many to have been part of the ancestral pool from which SARS-CoV-2 may have evolved 7, 8, 9. Multiple groups have been discussing the features of the genome sequence of the said strain. In this paper, we report that the currently specified level of details are grossly insufficient to draw inferences about the origin of SARS-CoV-2. De-novo assembly, KRONA analysis for metagenomic and re-examining data quality highlights the key issues with the RaTG13 genome and the need for a dispassionate review of this data. This work is a call to action for the scientific community to better collate scientific evidence about the origins of SARS-CoV-2 so that future incidence of such pandemics may be effectively mitigated.

The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Major Concerns on the Identification of Bat Coronavirus Strain RaTG13 and Quality of Related Nature Paper

A recent manuscript (Zhou, P. et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin”, Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7) from Wuhan Institute of Virology claimed the identification of a bat coronavirus, RaTG13, which showed 96.2% genome homology with SARS-CoV-2. In this paper, we raise the puzzling observations surrounding the identification, characterization, unique genome features of this RaTG13 strain, as well as its 100% nucleotide identity in partial RdRp gene with another bat coronavirus strain BtCoV/4991. And the paper presented premature hypothesis of potential bat origin of SARS-CoV-2 while RaTG13 strain was not successfully isolated. We also present the concerns on the methodology, data quality and experiment procedures described in this paper. We call for the authors to provide additional data, to share related samples to be verified and further characterized by other scientists.

Maintenance of species differences in closely related tetraploid parasitic Euphrasia (Orobanchaceae) on an isolated island

Polyploidy is pervasive in angiosperm evolution and plays important roles in adaptation and speciation. However, polyploid groups are understudied due to complex sequence homology, challenging genome assembly, and taxonomic complexity. Here we study adaptive divergence in taxonomically complex eyebrights (Euphrasia), where recent divergence, phenotypic plasticity and hybridisation blur species boundaries. We focus on three closely-related tetraploid species with contrasting ecological preferences, and which are sympatric on Fair Isle, a small isolated island in the British Isles. Using a common garden experiment, we show a genetic component to the morphological differences present between these species. Using whole genome sequencing and a novel k-mer approach, we demonstrate an allopolyploid origin, with sub-genome divergence of approximately 5%. Using ~2 million SNPs we show sub-genome homology across species consistent with a common origin, with very low sequence divergence characteristic of recent speciation. This genetic variation is broadly structured by species, with clear divergence of Fair Isle heathland E. micrantha, while grassland E. arctica and coastal E. foulaensis are more closely related. Overall, we show tetraploid Euphrasia is an allopolyploid system characterised by postglacial species divergence, where adaptation to novel environments may be conferred by old variants rearranged into new genetic lineages.

Misclassification of a whole genome sequence reference defined by the Human Microbiome Project: a detrimental carryover effect to microbiome studies

Taxonomic classification is an essential step in the analysis of microbiome data that depends on a reference database of whole genome sequences. Taxonomic classifiers are built on established reference species, such as the Human Microbiome Project database, that is growing rapidly. While constructing a population wide pangenome of the bacterium Hungatella, we discovered that the Human Microbiome Project reference species Hungatella hathewayi (WAL 18680) was significantly different to other members of this genus. Specifically, the reference lacked the core genome as compared to the other members. Further analysis, using average nucleotide identity (ANI) and 16s rRNA comparisons, indicated that WAL18680 was misclassified as Hungatella. The error in classification is being amplified in the taxonomic classifiers and will have a compounding effect as microbiome analyses are done, resulting in inaccurate assignment of community members and will lead to fallacious conclusions and possibly treatment. As automated genome homology assessment expands for microbiome analysis, outbreak detection, and public health reliance on whole genomes increases this issue will likely occur at an increasing rate. These observations highlight the need for developing reference free methods for epidemiological investigation using whole genome sequences and the criticality of accurate reference databases.

Chromosome-levelde novoassembly of the pig-tailed macaque genome using linked-read sequencing and HiC proximity scaffolding

Old world monkey species share over 93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them highly valuable animal models for the study of numerous human diseases. However, the quality of genome assembly and annotation for old world monkeys including macaque species lags behind the human genome effort. To close this gap and enhance functional genomics approaches, we employed a combination ofde novolinked-read assembly and scaffolding using proximity ligation assay (HiC) to assemble the pig-tailed macaque (Macaca nemestrina) genome. This combinatorial method yielded large scaffolds at chromosome-level with a scaffold N50 of 127.5 Mb; the 23 largest scaffolds covered 90% of the entire genome. This assembly revealed large-scale rearrangements between pig-tailed macaque chromosomes 7,12, and13 and human chromosomes 2, 14, and 15.