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ARC Journal of Urology
Volume-2 Issue-2, 2017, Page No: 12-16
DOI: http://dx.doi.org/10.20431/2456-060X.0202002

Codon Usage of Autosomal Dominant Polycystic Kidney Disease Genes PKD1 and PKD2

Li Gun*,Tian Han,Guo Rui,Du Ning

Department of Biomedical Engineering, School of Electronics and Information Engineering, Xi'an Technological University, Xi'an, Shaanxi Province, China.

Citation : Li Gun,et.al., "Codon Usage of Autosomal Dominant Polycystic Kidney Disease Genes PKD1 and PKD2". ARC Journal of Urology.2017;2(2):12-16.

Copyright : © 2017 . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract:

Objective: To investigate the codon characteristics in autosomal dominant polycystic kidney disease (ADPKD) genes PKD1 and PKD2. Differences between PKD1 and PKD2 are theoretically compared and their potential applications are discussed.

Methods: Codon gene sequences of PKD1 and PKD2 are downloaded from the gene bank: http://www.ncbi.nlm.nih.gov and their codon characteristics are predicted via the codonW system. The results of relative synonymous codon usage (RSCU) and A3 / (A3 + T3) vs. G3 / (G3 + C3) et al are plotted and discussed.

Results: The codon usage preferences of PKD1 and PKD2 are affected by mutations, and less affected by the selectively effect. The RSCU value of CUG and GUG in PKD1 are greater than 2. The RSCU value of CUC, UCC, CAG, GAG and UGA are among 1.5 to 2, and others are less than 1.5. The codon usage preference in the PKD2 is not bias like it in the PKD1. All the RSCU values in PKD2 are less than 1.5.

Conclusions: The relationship between the A3 / (A3 + T3) and G3 / (G3 + C3) obey the laws of nature, RSCU value of PKD1 is more than the value of PKD2 generally. All these information are important for studying the function of PKD1 and PKD2.

Keywords: Codon bias, PKD1, PKD2, ADPKD


1. Introduction

ADPKD is associated with large interfamilial and intrafamilial variability [1]. Many scientists studied the mechanism [2-5] of the ADPKD and its treatment from various methods [6-8]. Form the genome perspective, there are two mutations have been found to be associated with adpkd- PKD1 and PKD2 [9-12]. They are respectively on the 16th and 4th chromosomes [13-15]. Most of the ADPKD are caused by PKD1 mutation. Most of the patients with ADPKD may require dialysis or kidney transplantation eventually [16-18]. Therefore, it is necessary to study the ADPKD from the perspective of genome. Many scientists such as Tao Yang, et al, explored the novel mutations of PKD1 gene in Chinese patients with ADPKD by targeted next-generation sequencing [19], Consugar, et al. studied the characteristics of large rearrangements in ADPKD and the PKD1/TSC2 contiguous gene syndrome [20]. Furthermore, Pathogenicity [21], inactivation [22], development [23] of the PKD1 were also studied by many scientists. In this paper, based on the previous studies, the codon usage characteristics of PKD1 and PKD2 gene is cauculated via the CodonW, and analyzed via the PR2-bias plot analysis: A3 / (A3 + T3) vs. G3 / (G3 + C3) . Then the RSCU values of PKD1 and PKD2 are plotted and discussed.


2.Materials and Methods

Coding gene sequences of PKD1 and PKD2 are download from the website http://www.ncbi. nlm.nih.gov, and the accession numbers are: NC_000016.10:c2135898-2088708 and NC_00 0004.12:88007647-88077779. Then, the Codon W [24] is used to calculate the CAI, CBI, ENC and so on, the calculated results are further processed for getting the relative synonymous codon usage (RSCU), the PR2-bias plot analysis: A3 / (A3 + T3) vs. G3 / (G3 + C3), et al.


3. Results and Discussion

CodonW system is used to predict the codon usage characteristics of PKD1 and PKD2, and the overall results are shown in Table 1. in the table 1 Codon Adaptation Index (CAI) ranges from 0 to 1, the greater the value, the stronger the sub-preference of the codon and the higher the gene expression level, the CAI value of PKD1 is 0.17 and in PKD2 is 0.18 respectively, they are about the same. But when the Codon Bias Index (CBI) is concerned, their values are 0.05 and -0.08 respectively in PKD1 and PKD2. The values of effective codon number (ENC) are about the same in them. But there is a clear distinction for the content of GC.




The association between ENC and GC3 is shown in Figure 1. It can be seen that the PKD1 and PKD2 gene loci are distributed along the standard curve. The actual ENC values of KD1 and PKD2 genes are close to the expected ENC values, and locates of them are below the expected value. The codon usage preferences of PKD1 and PKD2 are affected by mutations, at the same time, the codon usage preferences is less affected by the selectively effect.


If there is no mutation in the two complementary strands of DNA, the base content should obey the law A = T and G = C. This method is usually used to analyze the PR2 bias occurring at the third place of the codon. The center of the graph follows the PR2 principle, A = T and G = C. The distance between the center (0.5, 0.5) and the plot dot represents the degree and direction of the PR2 bias. From the Figure 2, it can be seen that the content of pyrimidine (C + T) at the third position of the hemoglobin codon gene is equal to the purine content (A + G) in both PKD1 and PKD2.


Code preference is a common phenomenon in the evolutionary process. This phenomenon can not only reflect the evolution of biological groups, but also from the molecular level it can explain the basic phenomenon of biology, so it has very broad value of research and practical. The relative synonymous codon usage (RSCU) is an estimate of the preference for the use of synonymous codon, defined as the ratio of the observed value of the number of synonymous codons used to the expected value of occurrences of the codon. If the codon usage is not preferred, the RSCU value is 1; if a codon is used frequently, the RSCU value is greater than 1; if a codon usage frequency is low, the RSCU value is less than 1. The RSCU value intuitively reflects the preference for codon usage in PKD1 (Figure 3) and PKD2 (Figure 4) is calculated. In the Figure 3, it can be seen that in the PKD1, the codon usage preference of CUG and GUG are greater than 2. The codon usage preference of CUC, UCC, CAG, GAG and UGA are among 1.5 to 2. The codon usage preference others are less than 1.5. The value of RSCU is usually used as a measurement of the codon usage preference analysis.


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