11/21/2023 0 Comments Kozak consensus sequenceThis abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019. The identification of a novel translation initiation consensus in photoreceptor genes offers a new insight into the regulation of expression of these genes and provides an opportunity to consider the Kozak consensus use in AAV gene therapy vectors that target these cells. Of the 34 photoreceptor genes analysed, 29 carried nucleotides that differed to the original Kozak consensus at either the -4 or -2 position, or both. At the -2 position, nucleotide A was present in 41% of photoreceptor genes and 27% of vertebrate genes, the preference for which was C at the -2 position (49%). In vertebrate genes, the majority (53%) carried a C at the -4 position with the next most common nucleotide being A (25%), which is in contrast to the preference for G at this position in photoreceptor genes. An example of a Kozak consensus sequence is provided below. ![]() In photoreceptor genes, 51% carried a G at position -4 whereas in 699 vertebrate genes, 15% contained the G nucleotide. contain a Kozak translation initiation sequence with an ATG initiation codon for proper initiation of translation (Kozak, 1987 Kozak, 1991 Kozak, 1990). Comparisons of photoreceptor gene nucleotide frequencies revealed significant differences at positions -4 and -2 (p<0.0001 and p<0.007, respectively). Number of predictions (In order of decreasing. Sequence ID (Optional, default is QUERY). The consensus nucleotides of RPE genes from positions -12 to +4 matched those of the original Kozak consensus presented in 1987. take a list of the 133 sequences used for assessing Kozaks rule. The conserved frequencies of nucleotides at positions -12 to +4 were determined and compared to those identified by Marilyn Kozak at the respective positions in 699 genes from vertebrates using an independent chi-square test per nucleotide position. The ExAc database was used to identify known nucleotide variations at these positions. Consensus nucleotides from position -12 to +4 around the translation initiator codon ATG were extracted for all genes. Knowledge of the Kozak sequence in retinal genes may be important in the design of adeno-associated viral (AAV) vectors for retinal gene therapy.ĭata were compiled using the Geneious 10.0.9 software to review 26 human genes expressed in the retinal pigment epithelium (RPE) and 34 expressed in photoreceptor cells. The original Kozak consensus was defined by sequences identified in non-ocular tissues and, to date, the consensus for retinal genes remains unexplored. Alterations to the Kozak consensus influence gene translational efficiency and can cause disease. The Kozak consensus is a DNA sequence identified in eukaryotic genes that facilitates translation by identifying the start codon to ribosomes.
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