scholarly journals Codon clusters with biased synonymous codon usage represent hidden functional domains in protein-coding DNA sequences

2019 ◽  
Author(s):  
Zhen Peng ◽  
Yehuda Ben-Shahar

1.AbstractProtein-coding DNA sequences are thought to primarily affect phenotypes via the peptides they encode. Yet, emerging data suggest that, although they do not affect protein sequences, synonymous mutations can cause phenotypic changes. Previously, we have shown that signatures of selection on gene-specific codons usage bias are common in genomes of diverse eukaryotic species. Thus, synonymous codon usage, just as amino acid usage pattern, is likely a regular target of natural selection. Consequently, here we propose the hypothesis that at least for some protein-coding genes, codon clusters with biased synonymous codon usage patterns might represent “hidden” nucleic-acid-level functional domains that affect the action of the corresponding proteins via diverse hypothetical mechanisms. To test our hypothesis, we used computational approaches to identify over 3,000 putatively functional codon clusters (PFCCs) with biased usage patterns in about 1,500 protein-coding genes in the Drosophila melanogaster genome. Specifically, our data suggest that these PFCCs are likely associated with specific categories of gene function, including enrichment in genes that encode membrane-bound and secreted proteins. Yet, the majority of the PFCCs that we have identified are not associated with previously annotated functional protein domains. Although the specific functional significance of the majority of the PFCCs we have identified remains unknown, we show that in the highly conserved family of voltage-gated sodium channels, the existence of rare-codon cluster(s) in the nucleic-acid region that encodes the cytoplasmic loop that constitutes inactivation gate is conserved across paralogs as well as orthologs across distant animal species. Together, our findings suggest that codon clusters with biased usage patterns likely represent “hidden” nucleic-acid-level functional domains that cannot be simply predicted from the amino acid sequences they encode. Therefore, it is likely that on the evolutionary timescale, protein-coding DNA sequences are shaped by both amino-acid-dependent and codon-usage-dependent selective forces.

1995 ◽  
Vol 349 (1329) ◽  
pp. 241-247 ◽  

Silent sites (positions that can undergo synonymous substitutions) in protein-coding genes can illuminate two evolutionary processes. First, despite being silent, they may be subject to natural selection. Among eukaryotes this is exemplified by yeast, where synonymous codon usage patterns are shaped by selection for particular codons that are more efficiently and/or accurately translated by the most abundant tRNAs; codon usage across the genome, and the abundance of different tRNA species, are highly co-adapted. Second, in the absence of selection, silent sites reveal underlying mutational patterns. Codon usage varies enormously among human genes, and yet silent sites do not appear to be influenced by natural selection, suggesting that mutation patterns vary among regions of the genome. At first, the yeast and human genomes were thought to reflect a dichotomy between unicellular and multicellular organisms. However, it now appears that natural selection shapes codon usage in some multicellular species (e.g. Drosophila and Caenorhabditis ), and that regional variations in mutation biases occur in yeast. Silent sites (in serine codons) also provide evidence for mutational events changing adjacent nucleotides simultaneously.


2011 ◽  
Vol 57 (12) ◽  
pp. 1016-1023 ◽  
Author(s):  
Xue Lian Luo ◽  
Jian Guo Xu ◽  
Chang Yun Ye

In this study, we analysed synonymous codon usage in Shigella flexneri 2a strain 301 (Sf301) and performed a comparative analysis of synonymous codon usage patterns in Sf301 and other strains of Shigella and Escherichia coli . Although there was a significant variety in codon usage bias among different Sf301 genes, there was a slight but observable codon usage bias that could primarily be attributable to mutational pressure and translational selection. In addition, the relative abundance of dinucleotides in Sf301 was observed to be independent of the overall base composition but was still caused by differential mutational pressure; this also shaped codon usage. By comparing the relative synonymous codon usage values across different Shigella and E. coli strains, we suggested that the synonymous codon usage pattern in the Shigella genomes was strain specific. This study represents a comprehensive analysis of Shigella codon usage patterns and provides a basic understanding of the mechanisms underlying codon usage bias.


2013 ◽  
Vol 12 (1) ◽  
pp. 587-596 ◽  
Author(s):  
L. Chen ◽  
D.Y. Yang ◽  
T.F. Liu ◽  
X. Nong ◽  
X. Huang ◽  
...  

2012 ◽  
Vol 158 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Zhicheng Zhang ◽  
Wei Dai ◽  
Yang Wang ◽  
Chengping Lu ◽  
Hongjie Fan

2012 ◽  
Vol 60 (5) ◽  
pp. 461 ◽  
Author(s):  
Yuerong Zhang ◽  
Xiaojun Nie ◽  
Xiaoou Jia ◽  
Cunzhen Zhao ◽  
Siddanagouda S. Biradar ◽  
...  

Codon usage patterns of 23 Poaceae chloroplast genomes were analysed in this study. Neutrality analysis indicated that the codon usage patterns have significant correlations with GC12 and GC3 and also showed strong bias towards a high representation of NNA and NNT codons. The Nc-plot showed that although a large proportion of points follow the parabolic line of trajectory, several genes with low ENc values lie below the expected curve, suggesting that mutational bias played a major role in the codon biology of the Poaceae chloroplast genome. Parity Rule 2 plot analysis showed that T was used more frequently than A in all the genomes. Correspondence analysis of relative synonymous codon usage indicated that the first axis explained only a partial amount of variation of codon usage. Furthermore, the gene length and expression level were also found to drive codon usage variation. These findings revealed that besides natural selection, other factors might also exert some influences in shaping the codon usage bias in Poaceae chloroplast genomes. The optimal codons of these 23 genomes were also identified in this study.


Microbiology ◽  
2003 ◽  
Vol 149 (9) ◽  
pp. 2585-2596 ◽  
Author(s):  
Joshua T. Herbeck ◽  
Dennis P. Wall ◽  
Jennifer J. Wernegreen

Wigglesworthia glossinidia brevipalpis, the obligate bacterial endosymbiont of the tsetse fly Glossina brevipalpis, is characterized by extreme genome reduction and AT nucleotide composition bias. Here, multivariate statistical analyses are used to test the hypothesis that mutational bias and genetic drift shape synonymous codon usage and amino acid usage of Wigglesworthia. The results show that synonymous codon usage patterns vary little across the genome and do not distinguish genes of putative high and low expression levels, thus indicating a lack of translational selection. Extreme AT composition bias across the genome also drives relative amino acid usage, but predicted high-expression genes (ribosomal proteins and chaperonins) use GC-rich amino acids more frequently than do low-expression genes. The levels and configuration of amino acid differences between Wigglesworthia and Escherichia coli were compared to test the hypothesis that the relatively GC-rich amino acid profiles of high-expression genes reflect greater amino acid conservation at these loci. This hypothesis is supported by reduced levels of protein divergence at predicted high-expression Wigglesworthia genes and similar configurations of amino acid changes across expression categories. Combined, the results suggest that codon and amino acid usage in the Wigglesworthia genome reflect a strong AT mutational bias and elevated levels of genetic drift, consistent with expected effects of an endosymbiotic lifestyle and repeated population bottlenecks. However, these impacts of mutation and drift are apparently attenuated by selection on amino acid composition at high-expression genes.


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