Preliminary Analysis Of The Human Flanking Sequence Of The Gene Translation Of The Whole Story Location Features

In 1987, 5'-noncoding sequences have been compiled from 699 vertebrate mRNAs and analyzed by Kozak. "(GCC)GCCA/GCCATGG" emerges as the consensus sequence for initiation of translation in vertebrates. This conserved sequence flanking the ATG initiator codon has been designated "Kozak role". It plays an important role in the prediction of novel genes and research and development of biotechnological products. In the past 16 years, rapid progress has been made in life science and the number of known genes is increasing dramatically. Numerous gene sequences of different species have been deposited in various gene databases. However, the confirmation of "Kozak rule" based on large-scale level analysis was still unreported.In the current report, the Homo sapiens mRNA sequences in RefSeq database (http://www.ncbi.nlm.nih.gov/RefSeq/') were analyzed to explore the characteristic of the composition of bases flanking the ATG initiator codon in a large-scale level. At the same time, to investigate the rule of tandem repeat of codons, the arrangement of the stop codons in different frames was also analyzed.Using the home-made Perl programs, we extracted the concerned bases upstream and downstream of both the initiator codon and the stop codon for analysis. We found that first, the "Kozak rule" could be confirmed and extended efficiently. The bases in position -9 (nine nucleotides upstream from the ATG codon), -8, -6, -4, -3, -2, -1, +4, +5 and +6 were included in the rule. Second, the most highly conserved stop codon was TGA. Almost 50% of Homo sapiens mRNAs use TGA as the stop codon. The sequences flanking one kind of stop codon were different from another. The third, among the tandem arrayed stop codons in the same frame, the most highly frequent number of stop codons was two (the ratio was 94.83%), and then three and four. Among the two tandem stop codons, the most highly frequent was TGATGA. Tandem stop codons in differentframes were found in 522 mRNAs. Tandem initiator codons in the same frame and in different frames were found in 293 and 309 mRNAs, respectively, and most often 2 initiator codons arrayed tandem. In addition, another initiator codon ATG was found preceding the translation initiation site marked in 'CDS' in 35 mRNAs. We doubted the marker and it needs further investigation.It could be further inferred that the proteins in which stop codons arrayed tandem in the same frame might play an important role in the life decision. If the first stop codon was read through caused by mutation or misreading, the second stop codon could function and stop the translation. The tandem arrayed stop codons in different frame might take stage when base insert or deletion occurred in the coding region of mRNA.The current report focused on the codon usage analysis. The functional analysis and biological confirmation need to be performed in the future. Comparison of the above results with that of other model organisms will be also elucidated.