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Related Concept Videos

Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
From DNA to Protein03:06

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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...
Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.

D Allan Drummond1, Claus O Wilke

  • 1FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. dadrummond@cgr.harvard.edu

Cell
|July 30, 2008
PubMed
Summary

Selection against toxic misfolded proteins, caused by ribosome errors, explains gene evolution and expression patterns across species. This finding impacts understanding of molecular evolution and neurodegenerative diseases.

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Genetics

Background:

  • Consistent correlations exist between coding-sequence evolution rates and gene expression levels across taxa.
  • The underlying selective pressures driving these correlations are debated.
  • Previous studies noted trends in sequence evolution, codon usage, and mRNA levels, but a unified cause was unclear.

Purpose of the Study:

  • To demonstrate conserved patterns of covariation between sequence evolution, codon usage, and mRNA levels across diverse species.
  • To identify a unified selective pressure underlying these observed trends.
  • To propose and validate a molecular mechanism driving these evolutionary patterns.

Main Methods:

  • Comparative analysis of sequence evolution, codon usage, and mRNA levels in E. coli, yeast, worm, fly, mouse, and human.
  • Molecular-level evolutionary simulation to model the impact of ribosome errors and protein misfolding.
  • Analysis of trends in metazoan tissues, particularly neurons.

Main Results:

  • Conserved patterns of covariation were observed across all studied taxa, suggesting a unified selective pressure.
  • These trends were most pronounced in neuronal tissues, linked to sensitivity to protein misfolding.
  • A simulation demonstrated that selection against toxicity from misfolded proteins, arising from ribosome errors, can generate the observed covariation.

Conclusions:

  • Selection against toxicity of misfolded proteins is a primary driver of observed covariation between sequence evolution, codon usage, and mRNA levels.
  • The proposed model challenges the utility of nonsynonymous-to-synonymous substitution ratios (Ka/Ks) for detecting functional selection.
  • Mistranslation may play a significant role in the etiology of neurodegenerative diseases.