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Related Concept Videos

Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Transfer RNA Synthesis02:36

Transfer RNA Synthesis

One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

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Rare Event Detection Using Error-corrected DNA and RNA Sequencing
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SCUMBLE: a method for systematic and accurate detection of codon usage bias by maximum likelihood estimation.

Morten Kloster1, Chao Tang

  • 1Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, California 94158, USA.

Nucleic Acids Research
|May 23, 2008
PubMed
Summary

This study introduces a new statistical physics model to explain codon usage bias, revealing key factors influencing gene expression across species. The model accurately accounts for most codon usage variation in yeast and prokaryotes.

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Area of Science:

  • Genetics
  • Bioinformatics
  • Computational Biology

Background:

  • The genetic code is degenerate, with multiple codons encoding the same amino acid.
  • Synonymous codon usage varies significantly across species and genes, a phenomenon known as codon usage bias.
  • Existing methods explain only a fraction of observed codon usage variation.

Purpose of the Study:

  • To develop a novel model for codon usage bias inspired by statistical physics.
  • To identify and quantify different sources of codon bias in genomes.
  • To improve the understanding of factors influencing gene expression.

Main Methods:

  • Developed an explicit model of codon usage bias using principles from statistical physics.
  • Integrated the model with a maximum likelihood approach for data analysis.
  • Applied the algorithm to Saccharomyces cerevisiae and 325 prokaryotic genomes.

Main Results:

  • The statistical physics-based model effectively explains codon usage variation.
  • The approach clearly identifies diverse sources contributing to codon bias.
  • The model accounts for essentially all observed variance in most tested genomes.

Conclusions:

  • The new model provides a powerful framework for understanding codon usage bias.
  • This approach offers a more comprehensive explanation for codon bias than previous methods.
  • The findings have implications for gene expression regulation and synthetic biology.