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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and have instructions for its functioning. The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
Deoxyribonucleic Acid (DNA)
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
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In an SN2 reaction, the reaction rate depends on both the type of nucleophile and the substrate. A hindered tertiary alkyl halide is practically inert to the SN2 mechanism despite using a strong nucleophile.
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HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding.

Maria Nevot1, Ana Jordan-Paiz1, Glòria Martrus1

  • 1IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.

Journal of Virology
|June 8, 2018
PubMed
Summary
This summary is machine-generated.

Synonymously recoding the human immunodeficiency virus type 1 (HIV-1) protease altered resistance mutation patterns but not overall resistance levels. The recoded HIV-1 protease virus showed increased diversity, suggesting altered evolutionary pathways.

Keywords:
evolutionary biologyhuman immunodeficiency virusproteasessynonymous recoding

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Codon choice in viral genomes influences population diversity and evolvability.
  • Human immunodeficiency virus type 1 (HIV-1) protease is a key target for antiretroviral therapies.
  • Understanding HIV-1 resistance mechanisms is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate how synonymous recoding of the HIV-1 protease gene affects the development of resistance to protease inhibitors (PIs).
  • To compare the diversity and evolvability of wild-type (WT) HIV-1 and a codon-pair-reengineered variant (MAX) under PI selective pressure.

Main Methods:

  • Comparison of WT HIV-1 and MAX virus replication in cell cultures (MT-4 cells and PBMCs).
  • Serial passage of both viruses under selective pressure from atazanavir (ATV) and darunavir (DRV).
  • Ultradeep sequence clonal analysis to identify resistance mutations and assess viral diversity.

Main Results:

  • Both WT and MAX viruses developed phenotypic resistance to ATV and DRV after 32 passages.
  • Distinct repertoires of resistance mutations were observed between WT and MAX proteases.
  • The MAX virus exhibited significantly higher nucleotide and amino acid diversity, indicating increased evolvability.

Conclusions:

  • Synonymous recoding of the HIV-1 protease gene leads to different resistance mutation pathways but similar overall resistance levels.
  • The codon-reengineered HIV-1 protease variant demonstrates comparable mutational robustness and evolvability to the WT virus.
  • Synonymous recoding is a valuable tool for exploring viral genome architecture, evolutionary trajectories, and pathogenesis.