Gene: X最新文献

{"title":"Time-series analyses of directional sequence changes in SARS-CoV-2 genomes and an efficient search method for candidates for advantageous mutations for growth in human cells.","authors":"Kennosuke Wada, Yoshiko Wada, Toshimichi Ikemura","doi":"10.1016/j.gene.2020.100038","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100038","url":null,"abstract":"<p><p>We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100038"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-tracheal delivery of AAV6 vectors results in sustained transduction in murine lungs without genomic integration.","authors":"Yanerys Colon-Cortes, Mutasim Abu Hasan, George Aslanidi","doi":"10.1016/j.gene.2020.100037","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100037","url":null,"abstract":"<p><p>Despite the progress made in AAV-based gene therapy targeting different organ systems, lung-targeted gene therapy using AAV vectors has not been effective, mostly due to the poor transduction and un-sustained gene expression in airway epithelium. Furthermore, concerns over possible harmful insertional mutagenesis seen in other cell types, particularly hepatocytes, raised a question about AAV safety. In this study, we evaluate the long-term persistence of this vector in mouse lungs and any possible harmful integration of these vectors into the host genome. AAV6 vectors expressing reporter gene (firefly luciferase) were delivered to the lungs of C57BL/6 mice through intra-tracheal intubation. Despite the large variation among individual animals, most animals had high and sustained luciferase activity with a peak from 2 to 3 weeks post-transduction before a significant decline between 15 and 19 weeks post-transduction. More importantly, even after its decline, most animals maintained detectable luciferase expression for 150 days or more, which was confirmed by post-necropsy qPCR analysis of luciferase gene expression. At the termination point of experiments, an average of one copy of AAV expression cassette per mouse genome was detected. We also found that partial overlaps between the AAV6 expression cassette and the mouse genome were distributed broadly with no apparent systematic preference in any mouse chromosomal map location. In summary, our data suggest that AAV6 mediated long-term gene expression in the lungs with no evidence of genomic integration, and thus, any insertional mutagenesis.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100037"},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advance in circular RNA modulation effects of heart failure.","authors":"Li Jiang, Xiaoyan Wang, Xiaopeng Zhan, Sheng Kang, Haibo Liu, Yu Luo, Li Lin","doi":"10.1016/j.gene.2020.100036","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100036","url":null,"abstract":"<p><p>CircRNA (circular RNA) is a kind of closed circular structure of noncoding RNA molecules without 5' hat structure and 3' polyA, mainly located in the cytoplasm or stored in exosomes. It is not affected by RNA exonuclease, so it's stable and hard to be degraded. Proved to be widespread in a variety of eukaryotes, most circRNAs are cyclized by exons, some are lasso structures formed by intron cyclization. Recently, circRNAs have been demonstrated to play crucial roles in cardiomyocyte hypertrophy, fibrosis, autophagy and apoptosis, participating in the development of heart failure. There is increasing evidence that circRNAs may be a novel target for the treatment of heart failure.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100036"},"PeriodicalIF":0.0,"publicationDate":"2020-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splice2Deep: An ensemble of deep convolutional neural networks for improved splice site prediction in genomic DNA.","authors":"Somayah Albaradei, Arturo Magana-Mora, Maha Thafar, Mahmut Uludag, Vladimir B Bajic, Takashi Gojobori, Magbubah Essack, Boris R Jankovic","doi":"10.1016/j.gene.2020.100035","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100035","url":null,"abstract":"<p><strong>Background: </strong>The accurate identification of the exon/intron boundaries is critical for the correct annotation of genes with multiple exons. Donor and acceptor splice sites (SS) demarcate these boundaries. Therefore, deriving accurate computational models to predict the SS are useful for functional annotation of genes and genomes, and for finding alternative SS associated with different diseases. Although various models have been proposed for the in silico prediction of SS, improving their accuracy is required for reliable annotation. Moreover, models are often derived and tested using the same genome, providing no evidence of broad application, i.e. to other poorly studied genomes.</p><p><strong>Results: </strong>With this in mind, we developed the Splice2Deep models for SS detection. Each model is an ensemble of deep convolutional neural networks. We evaluated the performance of the models based on the ability to detect SS in <i>Homo sapiens</i>, <i>Oryza sativa japonica</i>, <i>Arabidopsis thaliana</i>, <i>Drosophila melanogaster</i>, and <i>Caenorhabditis elegans</i>. Results demonstrate that the models efficiently detect SS in other organisms not considered during the training of the models. Compared to the state-of-the-art tools, Splice2Deep models achieved significantly reduced average error rates of 41.97% and 28.51% for acceptor and donor SS, respectively. Moreover, the Splice2Deep cross-organism validation demonstrates that models correctly identify conserved genomic elements enabling annotation of SS in new genomes by choosing the taxonomically closest model.</p><p><strong>Conclusions: </strong>The results of our study demonstrated that Splice2Deep both achieved a considerably reduced error rate compared to other state-of-the-art models and the ability to accurately recognize SS in other organisms for which the model was not trained, enabling annotation of poorly studied or newly sequenced genomes. Splice2Deep models are implemented in Python using Keras API; the models and the data are available at https://github.com/SomayahAlbaradei/Splice_Deep.git.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100035"},"PeriodicalIF":0.0,"publicationDate":"2020-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced immortalization, <i>HUWE1</i> mutations and other biological drivers of breast invasive carcinoma in Black/African American patients.","authors":"Terrick Andey, Michael M Attah, Nana Adwoa Akwaaba-Reynolds, Sana Cheema, Sara Parvin-Nejad, George K Acquaah-Mensah","doi":"10.1016/j.gene.2020.100030","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100030","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Black/African-American (B/AA) breast cancer patients tend to have more aggressive tumor biology compared to White/Caucasians. In this study, a variety of breast tumor molecular expression profiles of patients derived from the two racial groupings were investigated. Breast invasive carcinoma sample data (RNASeq version 2, Reverse Phase Protein Array, mutation, and miRSeq data) from the Cancer Genome Atlas were examined. The results affirm that B/AA patients are more likely than Caucasian patients to harbor the aggressive &lt;i&gt;basal-like&lt;/i&gt; or the poor prognosis-associated &lt;i&gt;HER2-enriched&lt;/i&gt; molecular subtypes of breast cancer. There is also a higher incidence of the triple-negative breast cancer (TNBC) among B/AA patients than the general population, a fact reflected in the mutation patterns of genes such as &lt;i&gt;PIK3CA&lt;/i&gt; and &lt;i&gt;TP53&lt;/i&gt;. Furthermore, an immortalization signature gene set, is enriched in samples from B/AA patients. Among stage III patients, TERT, DRAP1, and PQBP1, all members of the immortalization gene signature set, are among master-regulators with increased activity in B/AA patients. Master-regulators driving differences in expression profiles between the two groups include immortalization markers, senescence markers, and immune response and redox gene products. Differences in expression, between B/AA and Caucasian patients, of &lt;i&gt;RB1&lt;/i&gt;, &lt;i&gt;hsa-let-7a&lt;/i&gt;, &lt;i&gt;E2F1&lt;/i&gt;, &lt;i&gt;c-MYC&lt;/i&gt;, &lt;i&gt;TERT&lt;/i&gt;, and other biomolecules appear to cooperate to enhance entry into the S-phase of the cell cycle in B/AA patients. Higher expression of &lt;i&gt;miR-221&lt;/i&gt;, an oncomiR that facilitates entry into the cell cycle S-phase, is regulated by &lt;i&gt;c-MYC&lt;/i&gt;, which is expressed more in breast cancer samples from B/AA patients. Furthermore, the cell migration- and invasion-promoting miRNA, &lt;i&gt;miR-135b&lt;/i&gt;, has increased relative expression in B/AA patients. Knock down of the immortalization marker &lt;i&gt;TERT&lt;/i&gt; inhibited triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) cell viability and decreased expression of TERT, MYC and WNT11. For those patients with available survival data, prognosis of stage II patients 50 years of age or younger at diagnosis, was distinctly poorer in B/AA patients. Also associated with this subset of B/AA patients are missense mutations in &lt;i&gt;HUWE1&lt;/i&gt; and &lt;i&gt;PTEN&lt;/i&gt; expression loss. Relative to Caucasian non-responders to endocrine therapy, B/AA non-responders show suppressed expression of a signature gene set on which biological processes including &lt;i&gt;signaling by interleukins&lt;/i&gt;, &lt;i&gt;circadian clock&lt;/i&gt;, &lt;i&gt;regulation of lipid metabolism by PPARα&lt;/i&gt;, &lt;i&gt;FOXO-mediated transcription&lt;/i&gt;, and &lt;i&gt;regulation of TP53 degradation&lt;/i&gt; are over-represented. Thus, we identify molecular expression patterns suggesting diminished response to oxidative stress, changes in regulation of tumor suppressors/facilitators, and enhanced immortalization in B/AA patients are likely important in defining the more aggressiv","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100030"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective functions of alternative splicing transcripts (<i>CdDHN4</i>-<i>L</i> and <i>CdDHN4</i>-<i>S</i>) of <i>CdDHN4</i> from bermudagrass under multiple abiotic stresses.","authors":"Di Zhang, Aimin Lv, Tianchen Yang, Xiaoqing Cheng, Enhua Zhao, Peng Zhou","doi":"10.1016/j.gene.2020.100033","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100033","url":null,"abstract":"<p><p>Dehydrins (DHNs) play critical roles in plant adaptation to abiotic stresses. The objective of this study was to characterize DHNs in bermudagrass (<i>Cynodon</i> spp.). <i>CdDHN4</i> gene was cloned from bermudagrass 'Tifway'. Two <i>CdDHN4</i> transcripts were detected due to alternative splicing (the nonspliced <i>CdDHN4</i>-<i>L</i> and the spliced <i>CdDHN4</i>-<i>S</i>) and both the CdDHN4-S and CdDHN4-L proteins are YSK₂-type DHNs, the Φ-segment is present in CdDHN4-L and absent in CdDHN4-S. Transgenic <i>Arabidopsis thaliana</i> expressing <i>CdDHN4</i>-<i>L</i> or <i>CdDHN4</i>-<i>S</i> exhibited improved tolerance to salt, osmotic, low temperature and drought stress compared to the wild type (WT). The two transgenic lines did not differ in salt or drought tolerance, while plants expressing <i>CdDHN4</i>-<i>S</i> grew better under osmotic stress than those expressing <i>CdDHN4</i>-<i>L</i>. Both transgenic lines exhibited reduced content of malondialdehyde (MDA) and reactive oxygen species (ROS); and higher antioxidant enzymatic activities than the wild type plants under salt or drought stress. <i>CdDHN4</i>-<i>S</i> exhibited a higher ROS-scavenging capacity than <i>CdDHN4</i>-<i>L</i>.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100033"},"PeriodicalIF":0.0,"publicationDate":"2020-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose and TNF enhance expression of <i>TNF</i> and <i>IL1B</i>, and histone H3 acetylation and K4/K36 methylation, in juvenile macrophage cells.","authors":"Kazue Honma, Chie Machida, Kazuki Mochizuki, Toshinao Goda","doi":"10.1016/j.gene.2020.100034","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100034","url":null,"abstract":"<p><p>Hyperglycemia activates innate leukocytes such as monocytes and induces pro-inflammatory cytokine expression, resulting in increased monocyte adhesion to aortic endothelial cells. In this study, we investigated whether high glucose and/or tumor necrosis factor (TNF) would enhance pro-inflammatory cytokine expression of <i>tumor necrosis factor</i> (<i>TNF</i>) and <i>interleukin (IL)-1β</i> (<i>IL1B</i>) by altering histone modifications in U937, a juvenile macrophage cell line. The mRNA levels of <i>TNF</i> and <i>IL1B</i> in U937 cells were significantly affected by glucose concentration and TNF treatment. Mono-methylated histone H3K4 signals around <i>TNF</i> and <i>IL1B</i> were lower in cells treated with high glucose compared with low glucose. Conversely, tri-methylated histone H3K4 and H3K36 signals were higher in cells treated with high glucose compared with low glucose. TNF treatment of U937 cells cultured in high glucose enhanced histone H3K36 tri-methylation, particularly around the gene regions of <i>TNF</i> and <i>IL1B</i>. Histone acetylation was induced by treatment with TNF in high-glucose medium. The induction of acetylation and tri-methylation of K4 and K36 of histone H3 around <i>TNF</i> and <i>IL1B</i> by treatment with high glucose and/or TNF was positively associated with the induction of these genes in juvenile macrophage U937 cells.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100034"},"PeriodicalIF":0.0,"publicationDate":"2020-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>ALCAM</i> (CD166) as a gene expression marker for human mesenchymal stromal cell characterisation.","authors":"Bas Brinkhof, Bo Zhang, Zhanfeng Cui, Hua Ye, Hui Wang","doi":"10.1016/j.gene.2020.100031","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100031","url":null,"abstract":"<p><strong>Background: </strong>Human mesenchymal stromal cells (MSCs) phenotypically share their positive expression of the International Society for Cell and Gene Therapy (ISCT) markers CD73, CD90 and CD105 with fibroblasts. Fibroblasts are often co-isolated as an unwanted by-product from biopsy and they can rapidly overgrow the MSCs in culture. Indeed, many other surface markers have been proposed, though no unique MSC specific marker has been identified yet. Quantitative PCR (qPCR) is a precise, efficient and rapid method for gene expression analysis. To identify a marker suitable for accurate MSC characterisation, qPCR was exploited.</p><p><strong>Methods and results: </strong>Two commercially obtained bone marrow (BM) derived MSCs and an hTERT immortalised BM-MSC line (MSC-TERT) have been cultured for different days and at different oxygen levels before RNA extraction. Together with RNA samples previous extracted from umbilical cord derived MSCs and MSC-TERT cells cultured in 2D or 3D, this heterogeneous sample set was quantitatively analysed for the expression levels of 18 candidate MSC marker genes. The expression levels in MSCs were compared with the expression levels in fibroblasts to verify the differentiation capability of these genes between MSCs and fibroblasts. None of the ISCT markers could differentiate between fibroblasts and MSCs. A total of six other genes (<i>ALCAM</i>, <i>CLIC1</i>, <i>EDIL3</i>, <i>EPHA2</i>, <i>NECTIN2</i>, and <i>TMEM47</i>) were identified as possible biomarkers for accurate identification of MSCs.</p><p><strong>Conclusion: </strong>Justified by considerations on expression level, reliability and specificity, Activated-Leukocyte Cell Adhesion Molecule (<i>ALCAM</i>) was the best candidate for improving the biomarker set of MSC identification.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100031"},"PeriodicalIF":0.0,"publicationDate":"2020-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse Ptchd3 is a non-essential gene.","authors":"Shaimar R González Morales, Chengjing Liu, Heath Blankenship, Guo-Zhang Zhu","doi":"10.1016/j.gene.2020.100032","DOIUrl":"https://doi.org/10.1016/j.gene.2020.100032","url":null,"abstract":"<p><p>Mouse Ptchd3 (patched domain containing 3) was previously identified as a male germ-cell specific gene. The protein product of this gene has been found on the surface of mouse, rat and human sperm. Since Ptchd3 contains a conserved patched domain, we hypothesize that it functions as a membrane receptor for the hedgehog ligand. Herein, we used a Ptchd3 knockout mouse model to study its function in mouse development and spermatogenesis. We found that Ptchd3 knockout mice were born and lived normally. The fertility and sperm production of knockout males were not changed. Moreover, our data indicated that the expression levels of several hedgehog signaling genes were not affected in mutant testis. Taken together, these findings demonstrate that Ptchd3 is a non-essential gene in mouse development and spermatogenesis.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100032"},"PeriodicalIF":0.0,"publicationDate":"2020-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interrogation of the cell wall integrity pathway in <i>Aspergillus niger</i> identifies a putative negative regulator of transcription involved in chitin deposition.","authors":"Tim M van Leeuwe, Mark Arentshorst, Peter J Punt, Arthur F J Ram","doi":"10.1016/j.gene.2020.100028","DOIUrl":"10.1016/j.gene.2020.100028","url":null,"abstract":"<p><p>Post-fermentation fungal biomass waste provides a viable source for chitin. Cell wall chitin of filamentous fungi, and in particular its de-<i>N-</i>acetylated derivative chitosan, has a wide range of commercial applications. Although the cell wall of filamentous fungi comprises 10-30% chitin, these yields are too low for cost-effective production. Therefore, we aimed to identify the genes involved in increased chitin deposition by screening a collection of UV-derived cell wall mutants in <i>Aspergillus niger</i>. This screen revealed a mutant strain (RD15.4#55) that showed a 30-40% increase in cell wall chitin compared to the wild type. In addition to the cell wall chitin phenotype, this strain also exhibited sensitivity to SDS and produces an unknown yellow pigment. Genome sequencing combined with classical genetic linkage analysis identified two mutated genes on chromosome VII that were linked with the mutant phenotype. Single gene knockouts and subsequent complementation analysis revealed that an 8 bp deletion in NRRL3_09595 is solely responsible for the associated phenotypes of RD15.4#55. The mutated gene, which was named <i>cwcA</i> (<i>cell wall chitin A</i>), encodes an orthologue of <i>Saccharomyces cerevisiae</i> Bypass of <i>ESS1</i> (<i>BYE1</i>), a negative regulator of transcription elongation. We propose that this conserved fungal protein is involved in preventing cell wall integrity signaling under non-inducing conditions, where loss of function results in constitutive activation of the cell wall stress response pathway, and consequently leads to increased chitin content in the mutant cell wall.</p>","PeriodicalId":37140,"journal":{"name":"Gene: X","volume":"5 ","pages":"100028"},"PeriodicalIF":0.0,"publicationDate":"2020-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}