Regularities of context-dependent codon bias in eukaryotic genes

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 N(1) context. We studied the relative abundance of codons with N(1) 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 N(1) context-dependent codon bias. The relative abundance of each codon with an N(1) 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 N(1) 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 N(1) context have a statistically significant correlation of their relative abundances.

密码子侧翼的核苷酸会影响同义密码子候选集中该特定密码子的选择。对密码子使用偏好影响最强的是紧邻密码子下游的核苷酸，该影响被称为N(1)语境（N(1) context）。我们针对全基因组已完成测序的四种真核生物——智人（Homo sapiens）、黑腹果蝇（Drosophila melanogaster）、秀丽隐杆线虫（Caenorhabditis elegans）以及拟南芥（Arabidopsis thaliana）——的基因，研究了带有N(1)语境的密码子的相对丰度。针对所有受试生物的分析显示，90%的密码子存在具有统计学显著性的N(1)语境依赖性密码子使用偏倚。我们将每个带有N(1)语境的密码子的相对丰度，与全基因组中相同的4核苷酸寡聚体（4mer oligonucleotide）的相对丰度进行了比对。该比对结果表明，约半数的语境依赖性密码子使用偏倚无法通过基因组的序列组成来解释。我们采用秩统计方法，对不同同义密码子组的语境依赖性密码子使用偏倚进行了比对。我们还发现了N(1)语境依赖性密码子使用偏倚与密码子核苷酸组成之间的规律性关联：第二、三位核苷酸一致且N(1)语境相同的密码子，其相对丰度具有统计学显著性的相关性。