Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution

BACKGROUND: Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV)-like sequences (ERTBVs) have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response. RESULTS: We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome. CONCLUSIONS: These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease

Rice transposable elements are characterized by various methylation environments in the genome

<p>Abstract</p> <p>Background</p> <p>Recent studies using high-throughput methods have revealed that transposable elements (TEs) are a comprehensive target for DNA methylation. However, the relationship between TEs and their genomic environment regarding methylation still remains unclear. The rice genome contains representatives of all known TE families with different characteristics of chromosomal distribution, structure, transposition, size, and copy number. Here we studied the DNA methylation state around 12 TEs in nine genomic DNAs from cultivated rice strains and their closely related wild strains.</p> <p>Results</p> <p>We employed a transposon display (TD) method to analyze the methylation environments in the genomes. The 12 TE families, consisting of four class I elements, seven class II elements, and one element of a different class, were differentially distributed in the rice chromosomes: some elements were concentrated in the centromeric or pericentromeric regions, but others were located in euchromatic regions. The TD analyses revealed that the TE families were embedded in flanking sequences with different methylation degrees. Each TE had flanking sequences with similar degrees of methylation among the nine rice strains. The class I elements tended to be present in highly methylated regions, while those of the class II elements showed widely varying degrees of methylation. In some TE families, the degrees of methylation were markedly lower than the average methylation state of the genome. In two families, dramatic changes of the methylation state occurred depending on the distance from the TE.</p> <p>Conclusion</p> <p>Our results demonstrate that the TE families in the rice genomes can be characterized by the methylation states of their surroundings. The copy number and degree of conservation of the TE family are not likely to be correlated with the degree of methylation. We discuss possible relationships between the methylation state of TEs and their surroundings. This is the first report demonstrating that TEs in the genome are associated with a particular methylation environment that is a feature of a given TE.</p

Full-endoscopic disc cleaning surgery

It has been reported that Modic change of the lumbar spine endplate includes three types: i.e. . edema or inflammation for type 1, fatty marrow change for type 2 and sclerotic change for type 3. Basically, type 1 Modic change may be related to the chronic low back pain. There are two kinds of the treatment for the type 1 Modic change to heal the pain : the anti-inflammatory drugs, and intra-discal injection of steroid. When the inflammatory change would be intractable, surgical intervention is needed. The gold standard for the surgical intervention is the segmental fusion of the affected level. The fusion surgery may cause the adjacent degeneration ; thus, motion preservation surgery is better, if possible. Our department started the motion preservation full-endoscopic intradiscal debridement surgery for this pathology, since some of the type 1 Modic change may be chronic discitis by P. Acnes. In this paper, we describe the first patient of type 1 Modic change who was successfully treated by the full-endoscopic intra-discal debridement and drainage under the local anesthesia. We named this procedure as transforaminal full-endoscopic disc cleaning surgery (FEDC). Finally, pathology, conservative and surgical intervention of Modic change was discussed

Mutation Analysis of 2009 Pandemic Influenza A(H1N1) Viruses Collected in Japan during the Peak Phase of the Pandemic

BACKGROUND: Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. METHODOLOGY: A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. RESULTS AND CONCLUSIONS: Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Alternative plant host defense against transposon activities occurs at the post-translational stage

The Antirrhinum DNA transposon Tam3 uniquely demonstrates low temperature-dependent transposition (LTDT), so transposition does not occur at high temperatures. We previously showed that the detainment of Tam3 transposase (TPase) at the plasma membrane occurs when transposition is inactive, and that TPase is released at the permissive state of Tam3 transposition. LTDT of Tam3 is attributed to interactions between Tam3 and its host. In this addendum, we propose a model to explain the LTDT of Tam3, which is regarded as an equilibrium state reached between the host and parasite to maximize the fitness of both

Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences

The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus-virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.Supporting information : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006413#sec01

DNA methylation is not necessary for the inactivation of the Tam3 transposon at non-permissive temperature in Antirrhinum

It has been proposed that DNA methylation plays an important role in the inactivation of transposons. This view stems from a comparison of the degree of methylation of transposons in the active and inactive state. However, direct evidence for the degree of methylation required for the suppression of transposition has not been reported. Transposon Tam3 in Antirrhinum majus undergoes somatic reversal of its transposition activity, which is tightly controlled by temperature: low temperature around 15℃ permits transposition, high temperatures around 25℃ strongly inhibits it. Our previous study had shown that the methylation state of the Tam3 end regions is negatively correlated with the Tam3 transposition frequency. The results of the present study reveal that the inactive state of Tam3 copies at high temperature is unlikely to be directly coupled to the methylation state. Treatment with methylation inhibitors (5-azacytidine or 5-azacytidine+ethionine) does not affect Tam3 excision frequency in calli derived from Antirrhinum hypocotyls. The results suggest that methylation is not essential for the suppression of Tam3 transposition at high temperature, but rather that some other mechanism(s) involved in the control of Tam3 transposition may be obscured by methylation

An apple atp9 pseudogene is maintained at high copy number in 'Golden Delicious'-type mitochondria but is present substoichiometrically in 'Delicious'-type mitochondria

In this study, the mitochondrial atp9 gene sequence of an apple cultivar 'Golden Delicious' was found to exist in one intact version and two truncated versions (termed φatp9-1 and φatp9-2). Interestingly, the φatp9-1 sequence is maintained at high copy number in the six 'Golden Delicious'-cytotype cultivars examined but present substoichiometrically in eight 'Delicious'-cytotype cultivars. Our data also suggest that φatp9-1 originated in a homologous recombination event mediated by the short repeat in a common ancestral mitochondrial genome of 'Golden Delicious' and 'Delicious', and was preferentially amplified in an evolutionary lineage that gave rise to the 'Golden Delicious'-type genome. On the other hand, φatp9-2 was revealed to be present in high abundance in all 14 cultivars examined