Regularities of context-dependent codon bias in eukaryotic genes

Abstract

Nucleotides surrounding a codon influence the choice of this particular codon from among the group of possible synonymous codons. The strongest influence on codon usage arises from the nucleotide immediately following the codon and is known as the N1 context. We studied the relative abundance of codons with N1 contexts in genes from four eukaryotes for which the entire genomes have been sequenced: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. For all the studied organisms it was found that 90% of the codons have a statistically significant N1 context-dependent codon bias. The relative abundance of each codon with an N1 context was compared with the relative abundance of the same 4mer oligonucleotide in the whole genome. This comparison showed that in about half of all cases the context-dependent codon bias could not be explained by the sequence composition of the genome. Ranking statistics were applied to compare context-dependent codon biases for codons from different synonymous groups. We found regularities in N1 context-dependent codon bias with respect to the codon nucleotide composition. Codons with the same nucleotides in the second and third positions and the same N1 context have a statistically significant correlation of their relative abundances.

Figure 1

Relative abundance of D.melanogaster codons with N₁ context and genomic oligonucleotides with context. Relative abundance of codons with N₁ context, R values were calculated using equation 1. Relative abundance of genomic oligonucleotides with context, r values were calculated as described in Materials and Methods. The ranking system is also described in Materials and Methods.

Figure 1

Relative abundance of D.melanogaster codons with N₁ context and genomic oligonucleotides with context. Relative abundance of codons with N₁ context, R values were calculated using equation 1. Relative abundance of genomic oligonucleotides with context, r values were calculated as described in Materials and Methods. The ranking system is also described in Materials and Methods.

Figure 2

D^AB values measuring the CDCB difference between groups A and B of synonymous codons with N₁ context. Groups of synonymous codons are marked by the letters of the amino acids they code for. Groups are divided into type I, II and III, based on their size and nucleotide composition in the third variable position. The tables present D values of pairwise comparisons for all groups of synonymous codons belonging to the same type. Synonymous group pairs with similar nucleotide compositions (having the same nucleotide in the second codon position) are boxed. Most frequently the minimal D values are located inside boxes and correspond to groups with similar nucleotide compositions. D values calculated for (A) D.melanogaster genes and (B) A.thaliana genes.

Figure 3

Cumulative probability distributions of D values for groups with randomly assigned ranks. The graphs can be used to assess the significance of D values. Specifically, the y-axis represents the probability that a pair of groups of 8 (A) or 16 (B) elements with randomly assigned ranks will have a D value less than or equal to the corresponding value on the x-axis.