Article
Microbiology
Fayna Diaz-San Segundo, Gisselle N. Medina, Edward Spinard, Anna Kloc, Elizabeth Ramirez-Medina, Paul Azzinaro, Steffen Mueller, Elizabeth Rieder, Teresa de los Santos
Summary: Foot-and-mouth disease is a significant viral disease affecting livestock, with live attenuated vaccines identified as one of the best options for early and long-lasting protection.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Virology
Zhen He, Shiwen Ding, Jiyuan Guo, Lang Qin, Xiaowei Xu
Summary: This study analyzed the phylogeny and codon usage pattern of narcissus viruses using the coat protein. The results showed that codon usage bias in these viruses is mainly influenced by natural selection, indicating the importance of evolutionary-based design for controlling these viruses.
Article
Biochemistry & Molecular Biology
Konrad Pawlak, Pawel Blazej, Dorota Mackiewicz, Pawel Mackiewicz
Summary: Synonymous codon usage is influenced by mutations and selection at both the nucleotide and amino acid levels. The proposed mutation-selection model demonstrates that the selection of amino acids based on physicochemical properties can result in biases in codon usage. Alternative genetic codes tend to exhibit greater codon bias than the standard genetic code, and the mutational pressures on cytosine and guanine content further affect usage bias. The study emphasizes the importance of considering amino acid selection in understanding codon usage patterns.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Shakibur Rahman, Sergei L. Kosakovsky Pond, Andrew Webb, Jody Hey
Summary: Research shows that synonymous codon substitutions are not always selectively neutral, and conventional dN/dS analyses may overestimate the frequency of positive diversifying selection and underestimate the strength of purifying selection. By analyzing two classes of synonymous substitutions, it was found that this discrepancy can be adequately explained by very weak selection with a mean product of population size and selection coefficient, Ns = 0.8.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Yi Liu, Qian Yang, Fangzhou Zhao
Summary: Codon usage bias affects gene expression levels and protein structures, influencing translation speed, accuracy, and the protein folding process. It also plays a key role in determining the proteome landscape. Furthermore, codon usage impacts mRNA levels through various effects on transcription and translation processes.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Biochemistry & Molecular Biology
Zishuo Zeng, Ariel A. Aptekmann, Yana Bromberg
Summary: Synonymous single nucleotide variants (sSNVs) are commonly overlooked but can have significant biological impact. The machine learning-based method synVep successfully distinguishes between pathogenic and benign variants with 90% precision and recall, without explicit conservation signals. It correlates with evolutionary distances in cross-species variation analysis.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Xukang Shen, Siliang Song, Chuan Li, Jianzhi Zhang
Summary: Synonymous mutations in protein-coding genes are not neutral and often result in reduced fitness and disturbed mRNA expression levels. Non-synonymous mutations have greater fitness variations across environments, which may explain the lower substitution rates compared to synonymous mutations.
Article
Biotechnology & Applied Microbiology
Christopher J. Giacoletto, Ronald Benjamin, Hong-Wen Deng, Jerome I. Rotter, Martin R. Schiller
Summary: The genetic code has degenerate codons that are generally thought to be silent, but some synonymous variants are not silent. In this study, we questioned the frequency of non-silent synonymous variants in HIV Tat transcription factor. We found that approximately 67% of synonymous variants in Tat were nonsilent, and 25% of them were associated with changes in codon usage, potentially affecting protein folding.
Article
Virology
Edward Spinard, Ian Fish, Paul A. Azzinaro, Monica Rodriguez-Calzada, Ethan J. Hartwig, George R. Smoliga, Aishwarya Mogulothu, Jonathan Arzt, Teresa de los Santos, Gisselle N. Medina
Summary: An in vitro assay was used to study recombination between wild-type and partially deoptimized live-attenuated vaccine candidates for foot-and-mouth disease. The results showed that recombination can occur within non-deoptimized viral genomic regions and that recombinants with large stretches of deoptimized or DIVA markers were less fit than wild-type viruses. This assay can be a valuable tool for designing improved codon deoptimized vaccine candidates.
Article
Biotechnology & Applied Microbiology
Jayanta Kumar Das, Swarup Roy
Summary: This study provides a comprehensive quantitative analysis of the protein-coding sequences of seven human coronaviruses, revealing the nucleotide sequence variability and codon usage patterns. Different categories of codons exhibit diverse adaptability, with notable variability in GC content at the third position among the seven coronaviruses. Phylogenetic analysis depicted the evolutionary relationships among these viruses and their positions in the tree.
Article
Biotechnology & Applied Microbiology
Alexander Schmitz, Fuzhong Zhang
Summary: Our study demonstrates that sequences with higher tRNA Adaptation Index (TAI) scores and Codon Adaptation Index (CAI) scores exhibit higher variation in green fluorescent protein (GFP) expression. This variation is not observed in sequences with high Normalized Translation Efficiency Index (nTE) scores or based on mRNA secondary structure folding energy. We found that noise in GFP expression scales with mean protein abundance for low-abundant proteins but remains constant for high-abundant proteins, suggesting that noise for high-abundance proteins is not primarily due to translation elongation. This indicates that codon optimization can be performed without worrying about gene expression noise in biotechnology applications.
Article
Immunology
Yu Fan, Duan Guo, Shangping Zhao, Qiang Wei, Yi Li, Tao Lin
Summary: This study aimed to explore the potential involvement of human genes with codon usage bias (CUB) similar to human polyomaviruses (HPyVs) genes in the pathogenesis of polyomavirus nephropathy (PVAN). The analysis revealed a significant correlation between HPyV genes and human genes, with a strong protein-protein interaction network. Gene expression analysis identified differentially expressed genes between normal kidney tissues and PVAN patients, which were involved in transcription, protein ubiquitination pathway, apoptosis, cellular response to stress, inflammation, and immune system. These findings may have implications for the diagnosis and treatment of HPyV-associated diseases, particularly PVAN.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xia Ran, Jinyuan Xiao, Fang Cheng, Tao Wang, Huajing Teng, Zhongsheng Sun
Summary: This study profiles tissue-specific codon optimality in human tissues and investigates the impact of synonymous mutations on codon optimality in human cancers. The findings suggest that optimal codon gain can promote tumor cell proliferation and serve as a prognostic biomarker in certain cancer types.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Genetics & Heredity
Wenjing Xu, Yingchun Li, Yajing Li, Chun Liu, Yanxia Wang, Guangmin Xia, Mengcheng Wang
Summary: Asymmetric somatic hybridization affects synonymous codon usage bias (SCUB) and promotes a bias towards A- and T-ending synonymous codons, with a stronger effect in indel-flanking sequences. This shift is attributed to whole genomic shock, and DNA methylation may play a role in SCUB shift during asymmetric somatic hybridization. Exogenous chromatin fragments introduced through this strategy do not have a local chromosomal effect on SCUB frequencies.
FRONTIERS IN GENETICS
(2021)
Article
Microbiology
Siqi Yang, Ye Liu, Xiaoyun Wu, Xiaofei Cheng, Xiaoxia Wu
Summary: The study reveals that Cowpea mild mottle virus has similar nucleotide compositions, prefers A/U-ending codons under the influence of natural selection. Its codon pattern is mainly shaped by the need to evade host antiviral responses and improve translational efficiency.
Article
Medicine, Research & Experimental
Zongliang Gao, Elena Herrera-Carrillo, Ben Berkhout
MOLECULAR THERAPY-NUCLEIC ACIDS
(2018)
Article
Medicine, Research & Experimental
Zongliang Gao, Elena Herrera-Carrillo, Ben Berkhout
MOLECULAR THERAPY-NUCLEIC ACIDS
(2018)
Article
Biochemistry & Molecular Biology
Zongliang Gao, Elena Herrera-Carrillo, Ben Berkhout
Article
Medicine, Research & Experimental
Zongliang Gao, Elena Herrera-Carrillo, Ben Berkhout
MOLECULAR THERAPY-NUCLEIC ACIDS
(2019)
Article
Biochemistry & Molecular Biology
Zongliang Gao, Ben Berkhout, Elena Herrera-Carrillo
Article
Medicine, Research & Experimental
Elena Herrera-Carrillo, Zongliang Gao, Ben Berkhout
MOLECULAR THERAPY-NUCLEIC ACIDS
(2019)
Article
Biochemistry & Molecular Biology
Zongliang Gao, Minghui Fan, Atze T. Das, Elena Herrera-Carrillo, Ben Berkhout
NUCLEIC ACIDS RESEARCH
(2020)
Article
Immunology
Bao-cun Zhang, Ramya Nandakumar, Line S. Reinert, Jinrong Huang, Anders Laustsen, Zong-liang Gao, Cheng-long Sun, Soren Beck Jensen, Anne Troldborg, Sonia Assil, Martin F. Berthelsen, Carsten Scavenius, Yan Zhang, Samuel J. Windross, David Olagnier, Thaneas Prabakaran, Chiranjeevi Bodda, Ryo Narita, Yujia Cai, Cong-gang Zhang, Harald Stenmark, Christine M. Doucet, Takeshi Noda, Zheng Guo, Raphaela Goldbach-Mansky, Rune Hartmann, Zhijian J. Chen, Jan J. Enghild, Rasmus O. Bak, Martin K. Thomsen, Soren R. Paludan
Correction
Immunology
Bao-cun Zhang, Ramya Nandakumar, Line S. Reinert, Jinrong Huang, Anders Laustsen, Zong-liang Gao, Cheng-long Sun, Soren Beck Jensen, Anne Troldborg, Sonia Assil, Martin F. Berthelsen, Carsten Scavenius, Yan Zhang, Samuel J. Windross, David Olagnier, Thaneas Prabakaran, Chiranjeevi Bodda, Ryo Narita, Yujia Cai, Cong-gang Zhang, Harald Stenmark, Christine M. Doucet, Takeshi Noda, Zheng Guo, Raphaela Goldbach-Mansky, Rune Hartmann, Zhijian J. Chen, Jan J. Enghild, Rasmus O. Bak, Martin K. Thomsen, Soren R. Paludan
Article
Biochemistry & Molecular Biology
Trine I. Jensen, Nanna S. Mikkelsen, Zongliang Gao, Johannes Fosselteder, Gabriel Pabst, Esben Axelgaard, Anders Laustsen, Saskia Konig, Andreas Reinisch, Rasmus O. Bak
Summary: This study developed CRISPRa and CRISPRi platforms based on RNA or ribonucleoprotein (RNP) delivery by electroporation, demonstrating transient and programmable gene regulation in primary cells such as human CD34(+) hematopoietic stem and progenitor cells and human CD3(+) T cells. These platforms provide simple and effective means for transiently controlling transcription, and can be easily applied and reprogrammed to new target genes using synthetic sgRNAs.
Article
Biotechnology & Applied Microbiology
Zongliang Gao, Sujan Ravendran, Nanna S. Mikkelsen, Jakob Haldrup, Huiqiang Cai, Xiangning Ding, Soren R. Paludan, Martin K. Thomsen, Jacob Giehm Mikkelsen, Rasmus O. Bak
Summary: Prime editing is a novel genome editing technology that allows for more efficient and precise editing of the genome. This study made advancements in improving editing efficiencies by optimizing the reverse transcriptase moiety and addressing limitations of viral vector size. These improvements resulted in a codon-optimized and size-minimized prime editor that showed superior editing efficiency in in vivo applications.
Article
Oncology
Eileen Wedge, Ulvi Ahmadov, Thomas B. Hansen, Zongliang Gao, Morten Tulstrup, Christophe Come, Sridhar Nonavinkere Srivatsan, Tanzir Ahmed, Jakob S. Jespersen, Balthasar C. Schlotmann, Claudia Schollkopf, Klas Raaschou-Jensen, Niels Odum, Jorgen Kjems, Rasmus O. Bak, Matthew J. Walter, Kirsten Gronbaek, Lasse S. Kristensen
Summary: Mutations in the U2AF1 gene are associated with a higher occurrence of myelodysplastic neoplasms (MDS) and a worse prognosis, but the exact molecular mechanisms are not fully understood. This study found that U2AF1 mutations may impact circRNA production, leading to increased cancer development. Increased circRNA expression levels were observed in cells and patient samples with U2AF1 mutations, suggesting a potential role of circRNA as a biomarker and therapeutic target in MDS.
Article
Biochemistry & Molecular Biology
Zongliang Gao, Yme Ubeles van der Velden, Minghui Fan, Cynthia Alyssa van der Linden, Monique Vink, Elena Herrera-Carrillo, Ben Berkhout
Summary: A newly engineered promoter variant was developed to enhance Pol III activity while reducing Pol II activity, providing a potential alternative to the commonly used H1 promoter. Small Pol II-specific H1 promoter variants were also explored for their potential use in protein expression. Safety concerns were addressed by designing promoter variants that exclusively express either Pol II or Pol III transcripts.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Meeting Abstract
Biotechnology & Applied Microbiology
Minghui Fan, Zongliang Gao, Elena Herrera-Carrillo, Ben Berkhout
Review
Biotechnology & Applied Microbiology
Elena Herrera-Carrillo, Zongliang Gao, Ben Berkhout
BRIEFINGS IN FUNCTIONAL GENOMICS
(2020)
