species-specific codon context rules unveil non-neutrality effects of synonymous mutations种特异的密码子上下文规则公布价值同义突变的影响.pdfVIP

Species-Specific Codon Context Rules Unveil Non-Neutrality Effects of Synonymous Mutations 1 2 3 ´ 2 ¨ 1 Gabriela R. Moura *, Miguel Pinheiro , Adelaide Freitas , Jose L. Oliveira , Jorg C. Frommlet , Laura 1 1 1 1 Carreto , Ana R. Soares , Ana R. Bezerra , Manuel A. S. Santos 1 RNA Biology Laboratory, Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal, 2 Institute of Electronics and Telematics Engineering (IEETA), University of Aveiro, Aveiro, Portugal, 3 Department of Mathematics, University of Aveiro, Aveiro, Portugal Abstract Background: Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution. Methodologies/Principal Findings: Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases. Conclusions: Since in vivo studies provide evidence for a role of codon context on