Codon preference

Eukaryotic DNA contains sequences recognized as termination signals in E. coli, resulting in premature termination of transcription and a truncated protein. Also, there are differences in codon preference affecting translation, which may ultimately... 

Organism-biased codon usage can be remedied by manipulating the interplay between a codon and its encoded amino acid. It is evident that several codons encode a particular amino acid, but only one amino acid is encoded by a particular codon. This redundancy is, thus, unidirectional in this context. Consequently, one could either increase the availability of the amino acid corresponding to the rare codon or change the transcript sequence to reflect the codon preferences of the host (analogous to market forces, one can either manipulate the supply or the demand sides). 

In the case of the P. falciparum genes that we analyzed here, we noted that the biases in base composition of different codon positions, amino acid frequencies and codon preferences are almost identical in housekeeping and antigen sequences. If we take into account that both the level of expression and the evolutionary constraints over these sequences are most unlikely to be the same, it is reasonable to conclude (i) that the extremely biased composition of the genome (Poliak et al., 1982 McCutchan et al., 1984) is the major factor in determining codon preferences and amino acid frequencies and (ii) that the compositional constraints (Bernardi and Bernardi, 1986a) operate in the same direction over all the translated sequences and their codon positions (Musto et al., 1995, 1997, 1999). 

Furthermore, while all Life uses the same genetic code, different species do have different codon preferences. In general, therefore, when designing a gene to be expressed in E. coli, the codon preferences for E. coli are used, whereas if the desire is to produce the polymer in tobacco, the codon preferences for tobacco are used. 

There are two basic reasons that allow delineation of reading or protein coding frames in nucleotide sequences, namely (1) the distribution of the 20 amino acids in proteins is not uniform and (ii) the degenerate but different codons for a particular amino acid are not uniformly selected. In other words, proteins display amino acid preferences and the coding sequences display codon preferences. These genetic facts result obviously in different expected frequencies for given codons and different expected positional base frequencies in the three codon nucleotide sites. As an example, the third position is almost uniformly occupied by the four bases as the amino acid code is generally insensitive to the nucleic acid selection at this site. 

Efficient translation depends on matching the preferred pattern of host codon usage in the heterologous gene. 

Analysis of the codon usage of the Clpgl sequence showed that 44 out of the 61 sense codons are used. Codons ending in C are preferred and represent 74.4 % of the codons used. 

In general, VFPs are preferred with optimized codon usage and containing folding mutations to facilitate expression and optimize maturation. 

Microparticles composed of each of four homopolyribonucleotides and the same lysine-rich proteinoid is found to influence the incorporation of individual amino-acyl adenylate 59). The incorporation favors the amino acids whose codons are related to the nucleotide in the particles (Fig. 6), when conditions are appropriately chosen. Other conditions yield other preferences. These results support a stereochemical basis for the genetic code. 

It is worthwhile to mention that a considerable degree of preference for certain codons has been observed for genes displaying high expression levels, which correlated with a higher abundance of the complementary tRNA in the cell (Fedorov et al., 2002). The optimization of codon usage... 

The term splicing refers to the process by which introns are removed and the mRNA put back together to form a continuous coding sequence in the 5 -3 direction. Remembering how accurate this process must be is important. If only a single nucleotide of an intron were left in the processed mRNA, the protein made from that mRNA would be non-functional, because the ribosome would read the wrong codons. The cellular machinery that splices pre-mRNAs uses information at the splice junctions to determine where to cut and where to rejoin the mRNA. Removal of introns from transcripts containing more than one intron usually occurs in a preferred but not exclusive order. Several pathways are used. 

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