Chithambaram Shivapriya, Prabhakaran Ramanandan, Xia Xuhua
Department of Biology and Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada.
Department of Biology and Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada
Mol Biol Evol. 2014 Jun;31(6):1606-17. doi: 10.1093/molbev/msu087. Epub 2014 Feb 27.
Because phages use their host translation machinery, their codon usage should evolve toward that of highly expressed host genes. We used two indices to measure codon adaptation of phages to their host, rRSCU (the correlation in relative synonymous codon usage [RSCU] between phages and their host) and Codon Adaptation Index (CAI) computed with highly expressed host genes as the reference set (because phage translation depends on host translation machinery). These indices used for this purpose are appropriate only when hosts exhibit little mutation bias, so only phages parasitizing Escherichia coli were included in the analysis. For double-stranded DNA (dsDNA) phages, both r(RSCU) and CAI decrease with increasing number of transfer RNA genes encoded by the phage genome. r(RSCU) is greater for dsDNA phages than for single-stranded DNA (ssDNA) phages, and the low r(RSCU) values are mainly due to poor concordance in RSCU values for Y-ending codons between ssDNA phages and the E. coli host, consistent with the predicted effect of C→T mutation bias in the ssDNA phages. Strong C→T mutation bias would improve codon adaptation in codon families (e.g., Gly) where U-ending codons are favored over C-ending codons ("U-friendly" codon families) by highly expressed host genes but decrease codon adaptation in other codon families where highly expressed host genes favor C-ending codons against U-ending codons ("U-hostile" codon families). It is remarkable that ssDNA phages with increasing C→T mutation bias also increased the usage of codons in the "U-friendly" codon families, thereby achieving CAI values almost as large as those of dsDNA phages. This represents a new type of codon adaptation.
由于噬菌体利用其宿主的翻译机制,它们的密码子使用情况应朝着高表达宿主基因的密码子使用情况演变。我们使用了两个指标来衡量噬菌体对其宿主的密码子适应性,即rRSCU(噬菌体与其宿主之间相对同义密码子使用情况[RSCU]的相关性)和以高表达宿主基因作为参考集计算的密码子适应性指数(CAI)(因为噬菌体翻译依赖于宿主翻译机制)。仅当宿主表现出很小的突变偏向性时,用于此目的的这些指标才适用,因此分析中仅纳入了寄生于大肠杆菌的噬菌体。对于双链DNA(dsDNA)噬菌体,r(RSCU)和CAI均随着噬菌体基因组编码的转运RNA基因数量的增加而降低。dsDNA噬菌体的r(RSCU)大于单链DNA(ssDNA)噬菌体,而ssDNA噬菌体的r(RSCU)值较低主要是由于ssDNA噬菌体与大肠杆菌宿主之间Y结尾密码子的RSCU值一致性较差,这与ssDNA噬菌体中C→T突变偏向性的预测效应一致。强烈的C→T突变偏向性会改善高表达宿主基因青睐U结尾密码子而非C结尾密码子的密码子家族(例如甘氨酸)中的密码子适应性(“U友好”密码子家族),但会降低高表达宿主基因青睐C结尾密码子而非U结尾密码子的其他密码子家族中的密码子适应性(“U敌对”密码子家族)。值得注意的是,具有增加的C→T突变偏向性的ssDNA噬菌体也增加了“U友好”密码子家族中密码子的使用,从而使CAI值几乎与dsDNA噬菌体的CAI值一样大。这代表了一种新型的密码子适应性。