Biologists have developed a model to determine the effect of synonymous codons on the synthesis of the encoded protein, according to the journal Nature.
A codon is a triplet of nucleotides (triplet) in DNA and messenger RNA, which encodes one amino acid in a protein. Since the number of codons encoding one of twenty amino acids is 61, some of the amino acids are encoded by several codons, which are called synonymous.
Synonymous codons can affect the level of protein expression in different ways, but finding out exactly what effect a particular codon will have is complicated by the fact that triplets also affect many structural features of messenger RNA. All these additional factors, in turn, can make different contributions to the efficiency of the gene translation process, and it becomes very difficult to determine the resulting effect.
To solve this problem, scientists have created a model that takes into account a wide range of features of the structure of RNA. For this, the level of protein expression was measured in 6 348 genes taken from various organisms (including humans) and introduced into E. coli cells. For each studied gene, the frequency of occurrence of all synonymous codons was measured, and the structural features of the messenger RNA corresponding to the gene were determined. Using the methods of regression analysis and modeling, scientists were able to figure out how specific codons, through additional factors, will affect the efficiency of RNA translation and protein synthesis.
The results showed that, in general, the direct influence of codons on expression exceeds the influence of additional factors; however, there are exceptions: the tertiary structure of messenger RNA near the front end of the molecule can completely stop the translation process. In addition, the data obtained confirmed that frequently occurring synonymous codons have a positive effect on the level of protein expression, primarily through the stabilization of RNA and an increase in its lifespan.
Scientists hope that the results of the study will help to create artificial genes, the synthesis of proteins which would be more efficient.
It is known that some synonymous codons in DNA coding regions occur more often than others. This phenomenon is called codon preference and was formed under the influence of evolution, when some codons had a more favorable effect on the efficiency of translation processes.