The relationship between synonymous codon usage and gene function, protein folding and protein structure

Genetic information is transferred in the form of triplet, also called genetic code or codon. It is well known that synonymous codons are often used with different frequencies. This phenomenon is called codon bias. The degree of codon bias has been found to be highly variable among genes from different species. Some researches show that there are high correlations between codon usage, tRNA abundance and gene expression. Most researches studied the gene codon usage in some lower species such as bacteria, yeast, C. Elegans, drosophila, Arabidopsis and so on. Few researches were focused on higher species such as rodent, primate animals and other mammals. Some researches were carried on to study the codon usage of genes in organelles. Morton studied the codon usage of genes in chloroplast in plants and found that the codon usage was divergent between chloroplast genes in land plants. To reveal the relationship between protein function and codon usage bias, we should extensively study the codon use frequencies of genes with different functions and from different species. Several methods have been used to study the gene codon bias in different species. The relative synonymous codon use frequencies (RSCU) of 135 MHC genes from four mammal species are analyzed using hierarchical cluster method. The result suggests that gene function is the dominant factor that determines codon usage bias, while species is a minor factor that determines further difference in codon usage bias for genes with similar functions. Recent studies suggest that codon usage is related to protein secondary structure. Ding et al found that there WEIS no significant correlation between codon usage and protein secondary structure in E. coli, but there might be a correlation in mammals. Although many studies have been performed to look for the relationship between codon usage and protein secondary structure, yet few researches are focused on the relationship between codon usage and protein super-secondary structure, and further more the tertiary structure. 195 genes coding for proteins in four different folding types have been analyzed in terms of variance analysts, in which there are 50 genes coding for all alpha proteins, 66 entries for all beta proteins, 37 entries for alpha+beta proteins and 42 entries for alpha/beta proteins. We have observed that codon usage in different gene classes coding for differently folded proteins is significantly different. Similar to amino acid propensities in different protein classes, folding type specific proteins have specific codon usage patterns. With the help of codon usage pattern in different protein classes, we can improve the accuracy of prediction of protein folding type and further prediction of protein secondary structure. At the same time, RSCU values of 71 genes coding for proteins with two different fingerprints are also studied and these 71 genes can be clearly differentiated into two groups according to the difference in codon usage bias. This indicates that codon usage is closely related to the high-level structure of protein.