IMPACT OF tAI IN TRANSLATIONAL DYNAMICS OF HOMO SAPIENS GENES IN ESCHERICHIA COLI GENOME

摘要

Objective: Translation of mRNA to protein is a central biological process, and its regulation is vital for cell growth, development and differentiation. It is known that the tRNA molecules play a role of nearly 40% in the process of translation. The objective of this study was to find out the major DNA and protein determinants that play major role in heterologous expression of human genes in a prokaryote ( E. coli K12 strain) for pharmaceutical applications. Methods: In this article, we have analyzed the expression of 40 randomly chosen genes of Homo sapiens in E. coli K12 strain with tAI (tRNA adaptation index) as an expression measure in the background of E. coli tRNA gene pool using bioinformatic tools. We have studied how three major local features of a gene’s coding sequence (namely coding sequence adaptation to the tRNA pool, nuleobases at three positions in codons and codon encoded-amino acid) affect the translation elongation process. Results: Correlation analysis revealed T3 (r = 0.52**), and T1 (r= 0.51**) are positively correlated with tAI. The anticodon of tRNA genes refers the nucleobase T in the mRNA for translation efficiency. Moreover, AT1 (r= 0.28) and GC2 (r= 0.18) contents showed positive correlation with tAI indicating the role of AT composition at first position and the GC composition at third position of codon in human transgene expression in a bacterium. Several amino acids namely, Asp, Ile, Thr and Tyr showed highly significant positive correlation with tAI. Conclusion: Our results suggest that nucleobase compositional dynamics is a determinant of transcriptional dynamics in heterologous gene expression. Keywords : tAI- tRNA Adaptation Index, Translational activity, Synonymous codons, Gene expression.