Genes & Genetic Systems
Online ISSN : 1880-5779
Print ISSN : 1341-7568
ISSN-L : 1341-7568
Advance online publication
Displaying 1-6 of 6 articles from this issue
  • Yuta Inoue, Hitoshi Suzuki
    Article type: Full paper
    Article ID: 21-00079
    Published: 2022
    Advance online publication: June 25, 2022
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    We have previously estimated the evolutionary rate (number of substitutions/site/million years) of mitochondrial cytochrome b gene (Cytb) sequences in rodents and moles to be about 0.11 at more recent divergence times of tens of thousands of years, and to decrease rapidly to about 0.03 at more distant divergence times. Because this time dependency is thought to be caused by the removal of mildly deleterious substitutions in later generations, we focused in this study on the abundance of nonsynonymous substitutions. We collected 23 haplogroups of Cytb with signals of late Quaternary population expansion events from rodents and moles and categorized them into three groups for comparison based on predicted expansion start time: 5,000–15,000 years ago (Group I), ca. 53,000 years ago (Group II) and 130,000–230,000 years ago (Group III). We counted the numbers of nonsynonymous and synonymous substitutions in all haplogroups. The rates of nonsynonymous substitutions were lowest in Groups II and III (0.08–0.22), whereas those in Group I varied markedly. We further classified Group I into two subgroups based on high (0.29–0.43) and low (0.09–0.20) nonsynonymous substitution rates, which were likely to be associated with the start of the expansion within 10,000 years and at around 15,000 years ago, respectively. The Group II and III networks had two- or three-step star-shaped structures and tended to exhibit frequent and less frequent nonsynonymous substitutions on exterior and interior branches, respectively. Based on temporal dynamics, nonsynonymous mitochondrial DNA (mtDNA) substitutions in small mammals accounted for at most 40% of all substitutions during the early evolutionary stage and then rapidly declined, dropping to approximately 15%. The results of this study provide a good explanation of the time-dependent trend in the mtDNA evolution rate predicted in previous work.

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  • Masaki Shirai, Takuya Nara, Haruko Takahashi, Kazuya Takayama, Yuan Ch ...
    Article type: Full paper
    Article ID: 21-00092
    Published: 2022
    Advance online publication: June 18, 2022
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    Supplementary material

    CpG methylation of genomic DNA is a well-known repressive epigenetic marker in eukaryotic transcription, and DNA methylation of promoter regions is correlated with gene silencing. In contrast to the promoter regions, the function of DNA methylation during transcription termination remains to be elucidated. A recent study revealed that mouse DNA methyltransferase 3a (Dnmt3a) mainly functions in de novo methylation in the promoter and gene body regions, including transcription termination sites (TTSs), during development. To investigate the relationship between DNA methylation overlapping the TTSs and transcription termination, we performed bioinformatics analysis using six pre-existing Dnmt-/- mouse cell datasets: four types of neurons (three Dnmt3a-/- and one Dnmt1-/- mutants) and two types of embryonic fibroblasts (MEFs) (Dnmt3a-/- and Dnmt3b-/- mutants). Combined analyses using methylome and transcriptome data revealed that read counts downstream of hypomethylated TTSs were increased in three types of neurons (two Dnmt3a-/- and one Dnmt1-/- mutants). Among these, an increase in chimeric transcripts downstream of the TTSs was observed in Dnmt3a-/- mature olfactory sensory neurons and Dnmt3a-/- agouti-related peptide (protein)-producing neurons, thereby indicating that read-through occurs in hypomethylated TTSs at specific gene loci in these two mutants. Conversely, in Dnmt3a-/- MEFs, we detected reductions in read counts downstream of hypomethylated TTSs. These results indicate that the hypomethylation of TTSs can both positively and negatively regulate transcription termination, dependent on Dnmt and cell types. This study is the first to identify the aberrant termination of transcription at specific gene loci with DNA hypomethylated TTSs attributable to Dnmt deficiency.

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  • Ze-Liang Lin, Yan-Cun Liu, Yu-Lei Gao, Xin-Sen Chen, Chao-Lan Wang, So ...
    Article type: Full paper
    Article ID: 21-00073
    Published: 2022
    Advance online publication: June 09, 2022
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    Supplementary material

    Acute myocardial infarction (AMI) is one of the leading causes of death globally, with a mortality rate of over 20%. However, the diagnostic biomarkers frequently used in current clinical practice have limitations in both sensitivity and specificity, likely resulting in delayed diagnosis. This study aimed to identify potential diagnostic biomarkers for AMI and explored the possible mechanisms involved. Datasets were retrieved from the Gene Expression Omnibus. First, we identified differentially expressed genes (DEGs) and preserved modules, from which we identified candidate genes by LASSO (least absolute shrinkage and selection operator) regression and the SVM–RFE (support vector machine–recursive feature elimination) algorithm. Subsequently, we used ROC (receiver operating characteristic) analysis to evaluate the diagnostic accuracy of the candidate genes. Thereafter, functional enrichment analysis and an analysis of immune infiltration were implemented. Finally, we assessed the association between biomarkers and biological processes, infiltrated cells, clinical traits, tissues and time points. We identified nine preserved modules containing 1,016 DEGs and managed to construct a diagnostic model with high accuracy (GSE48060: AUC = 0.923; GSE66360: AUC = 0.973) incorporating two genes named S100A9 and SOCS3. Functional analysis revealed the pivotal role of inflammation; immune infiltration analysis indicated that eight cell types (monocytes, epithelial cells, neutrophils, CD8+ T cells, Th2 cells, NK cells, NKT cells and platelets) were likely involved in AMI. Furthermore, we observed that S100A9 and SOCS3 were correlated with inflammation, variably infiltrated cells, clinical traits of patients, sampling tissues and sampling time points. In conclusion, we suggested S100A9 and SOCS3 as diagnostic biomarkers of AMI and discovered their association with inflammation, infiltrated immune cells and other factors.

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  • Ranhong Li, Jingjing Sun, Xiaomeng Ning, Dan Liu, Xin Chen
    Article type: Full paper
    Article ID: 21-00098
    Published: 2022
    Advance online publication: June 09, 2022
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    Pathogen attacks affect tree health, causing considerable economic losses as well as serious damage to the surrounding environment. Understanding the disease resistance mechanisms of trees is important for tree breeding. In previous studies on birch (Betula platyphylla × B. pendula), we identified a lesion mimic mutant called lmd. We found that reduced expression of BpEIL1 was responsible for the phenotype in lmd. Following cloning, we acquired several BpEIL1 overexpression and suppression lines in birch. In this study, we cloned the BpEIL1 promoter and found that BpEIL1 was primarily expressed in leaves, particularly in veins. We further studied the traits of transgenic lines and the function of BpEIL1 in disease resistance in birch using the BpEIL1 overexpression line OE9, the suppression line SE13 and the non-transgenic line NT. We found that hydrogen peroxide accumulated in SE13 leaves. Ascorbate peroxidase and catalase activity significantly increased in SE13. SE13 was more resistant to the fungal pathogens Alternaria alternata and Rhizoctonia solani than were the OE9 and NT lines. RNA-seq indicated that pathways related to signal transduction, disease resistance and plant immunity were enriched in SE13. BpEIL1 is thus a negative regulatory transcription factor for disease resistance in birch. This study provides a reference for disease resistance of birch and other trees.

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  • Qin Zhao, Zhijing Ge, Suhong Fu, Sha Wan, Jing Shi, Yunhong Wu, Yongqu ...
    Article type: Full paper
    Article ID: 21-00006
    Published: 2022
    Advance online publication: May 28, 2022
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    The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein–protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.

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  • Koki Nagasawa, Shigeru Fukumoto, Hiroaki Setoguchi, Masae Ishihara, Ke ...
    Article ID: 21-00087
    Published: 2022
    Advance online publication: May 12, 2022
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    Interspecific hybridization is a critical issue in conservation biology because it may drive small populations to extinction through direct or indirect processes. In this study, to develop a conservation strategy for an endangered rear-edge population of Carex podogyna in Ashiu, Kyoto, Japan, we performed a molecular genetic analysis of the wild population and an ex-situ population established from wild seeds. Microsatellite genotypic data revealed a complete loss of genetic diversity in the wild population, suggesting that it has long been prone to genetic drift due to isolation as a small population. In contrast, microsatellite analysis of 13 ex-situ individuals detected multiple alleles that are not harbored in the wild C. podogyna population. Sequence analysis revealed that these individuals are likely natural hybrids between C. podogyna and a co-occurring species, C. curvicollis, although established hybrids have never been found in the natural habitat. Based on our observation of variegated leaves in hybrid individuals, we propose that hybrids have been excluded by natural selection and/or interspecific competition caused by insufficient productivity of photosynthesis, although other genetic and ecological factors may also be influential. Overall, this study indicates that natural mechanisms selectively removing the hybrids have maintained the genetic purity of this rear-edge population of C. podogyna, and also emphasizes the importance of genetic assessment in ex-situ conservation programs.

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