Protein Coding


A protein‐coding gene is composed of a series of nucleotide triplets – the codons – that encrypt not only the protein content but also the start and stop signals. There are 64 (43) codons in the canonical genetic code, which encode 20 amino acids with redundancy. Hence, there are synonymous codons that encode the same amino acids, and they are used at different frequencies among different species. The resultant codon‐usage biases reveal complex interplays of mutation and selection. Protein‐coding genes can be organised into families of similar function, structure and sequence, according to their shared evolutionary histories. Individual proteins are modularly constructed of domains, which are often rearranged on evolutionary timescales to create functionally novel proteins.

Key Concepts:

  • A protein‐coding gene consists of a series of nucleotide triplets.

  • The genetic code defines the relationship between codons and amino acids.

  • The genetic code can be organised into two halves and four quarters, which manifest distinct physiochemical features.

  • Codon usage bias, a phenomenon in which synonymous codons (encoding the same amino acid) are used at different frequencies in different species, is a result of complex interplays between mutation and selection.

  • Protein‐coding genes are organised into families of similar function, structure and sequence, according to their shared evolutionary histories.

  • Individual proteins are modularly constructed from domains, which are often rearranged on evolutionary timescales to create functionally novel proteins.

Keywords: genetic code; codon usage; gene family; domain; alternative splicing

Figure 1.

A content‐centric organisation of the genetic code based on GC and purine contents. The genetic code is divided into two halves (shaded in light pink and blue) and four quarters (letters highlighted in blue, green, orange and red). R and Y stand for purine and pyrimidine, respectively. N represents any of the four nucleotides and St indicates stop codon.

Figure 2.

Effective number of codons plotted against G+C content at the third codon position, with one point for each of the 7765 experimentally confirmed human genes. The line is a theoretical upper bound that is based on the genetic code.

Figure 3.

Amino acid identities in the globin superfamily. The matrix element M(I, J) refers to the number of identically matched amino acids between row I and column J, given as a percentage of the protein found in row I.

Figure 4.

Number of distinct domain architectures in the first four sequenced eucaryotic genomes, shown according to cellular environment as intracellular, extracellular and transmembrane. Adapted with permission from Lander et al. .

Figure 5.

Alternative splice forms for NRXN3. Different versions of an exon are indicated by a letter suffix. All conceivable exon combinations are listed with an ‘y’ (yes) or ‘n’ (no) to indicate whether or not it has been observed.



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Zhang, Zhang, Wong, Gane Ka‐Shu, and Yu, Jun(Jun 2013) Protein Coding. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005017.pub2]