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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...
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Triphasic Development of the Genetic Code.

Tze-Fei Wong1

  • 1Division of Life Science and Applied Genomics Center, Hong Kong University of Science & Technology Hong Kong, China.

Chemical Reviews
|August 1, 2024
PubMed
Summary

The genetic code, initially limited to 20 amino acids, was frozen due to biological constraints. Scientists have now developed methods to encode new noncanonical amino acids (ncAAs), expanding the genetic alphabet beyond its original limits.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The standard genetic code utilizes 20 amino acids, categorized into Phase 1 (prebiotic availability) and Phase 2 (biosynthesis-dependent).
  • The genetic code was "frozen" early in evolutionary history, with organisms like *Methanopyrus kandleri* showing no expansion of the amino acid alphabet for billions of years.
  • This "freezing" is attributed to oligogenic barriers, where organisms become highly adapted to the standard 20 amino acids, making deletions detrimental to viability.

Purpose of the Study:

  • To explain the evolutionary reasons behind the "frozen" state of the genetic code.
  • To highlight the development and success of methods for encoding novel noncanonical amino acids (ncAAs).
  • To underscore the expansion of the genetic code beyond the 20 canonical amino acids.

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Main Methods:

  • Historical analysis of genetic code evolution and organismal adaptation.
  • Review of scientific discoveries explaining the "freezing" of the genetic code.
  • Description of methodologies enabling the encoding of noncanonical amino acids (ncAAs).

Main Results:

  • The genetic code's initial 20 amino acids were limited by prebiotic availability and later biosynthesis.
  • Oligogenic barriers prevent the removal of any standard amino acid, preserving the code's structure.
  • Scientists have successfully devised procedures to encode novel noncanonical amino acids (ncAAs), expanding the genetic repertoire.

Conclusions:

  • The evolutionary trajectory of the genetic code was shaped by environmental availability and biological adaptation.
  • Understanding the constraints of the "frozen" code paved the way for scientific innovation.
  • The successful encoding of Phase 3 noncanonical amino acids represents a significant expansion beyond the traditional 20 amino acids.