Genome-wide mutations and selection within a population are the basis of natural evolution. A similar process occurs during antibody affinity maturation when immunoglobulin genes are hypermutated and only those B cells which express antibodies of improved antigen-binding specificity are expanded. Protein evolution might be simulated in cell culture, if transgene-specific hypermutation can be combined with the selection of cells carrying beneficial mutations. Here, we describe the optimization of a GFP transgene in the B cell line DT40 by hypermutation and iterative fluorescence activated cell sorting. Artificial evolution in DT40 offers unique advantages and may be easily adapted to other transgenes, if the selection for desirable mutations is feasible.
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http://dx.doi.org/10.1093/nar/gkm616 | DOI Listing |
IUBMB Life
January 2025
Department of Biology, Pomona College, Claremont, California, USA.
All life depends on accurate and efficient protein synthesis. The aminoacyl-tRNA synthetases (aaRSs) are a family of proteins that play an essential role in protein translation, as they catalyze the esterification reaction that charges a transfer RNA (tRNA) with its cognate amino acid. However, new domains added to the aaRSs over the course of evolution in eukaryotes confer novel functions unrelated to protein translation.
View Article and Find Full Text PDFSignal Transduct Target Ther
December 2024
School of Basic Medical Science, Tsinghua University, 30 Shuangqing Rd., Haidian District, Beijing, 100084, China.
Modeling and predicting mutations are critical for COVID-19 and similar pandemic preparedness. However, existing predictive models have yet to integrate the regularity and randomness of viral mutations with minimal data requirements. Here, we develop a non-demanding language model utilizing both regularity and randomness to predict candidate SARS-CoV-2 variants and mutations that might prevail.
View Article and Find Full Text PDFJ Pharm Sci
December 2024
Biologics Quality & Regulatory Consultants, LLC, North Potomac, MD, 20878, USA. Electronic address:
Biological Standardization has been pivotal to the success of traditional biological products, such as vaccines, antitoxins, and immune globulins, by ensuring their quality and consistency across manufacturers worldwide. The principles of biological standardization have similarly supported the development and manufacture of safe and effective modern biological products, including hormone, therapeutic protein, and monoclonal antibody products, and continue to play a vital role in advancing new cutting-edge biological products, such as tissue, cellular, and gene-therapy products. Biological standardization started with the physical standards ensuring the reliability and suitability of methods used to test biological products and science of bioassays or biological methods and related biostatistics providing a framework for evaluating biological, functional activity or potency of these products.
View Article and Find Full Text PDFAnaesth Crit Care Pain Med
December 2024
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; University of Barcelona (UB), Barcelona, Spain; Respiratory Intensive Care Unit, Pneumology, Respiratory Institute, Hospital Clinic of Barcelona, Barcelona, Spain. Electronic address:
Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Peoples' Friendship University of Russia, Moscow, 117198 Russia.
The E6 and E7 proteins of the high risk human papillomaviruses (HR HPVs) play a key role in the oncogenesis associated with papillomavirus infection. Data on the variability of these proteins are limited, and the factors affecting their variability are still poorly understood. We analyzed the variability of the currently known sequences of the HPV type 16 (HPV16) E6 and E7 proteins, taking into account their geographic origin and year of sample collection, as well as the direction of their evolution in the major geographic regions of the world.
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