title: How do variable substitution rates influence Ka and Ks calculations?
abstract: The ratio of nonsynonymous substitution rate (Ka) to synonymous substitution rate (Ks) is widely used as an indicator of selective pressure at sequence level among different species, and diverse mutation models have been incorporated into several computing methods. We have previously developed a new gamma-MYN method by capturing a key dynamic evolution trait of DNA nucleotide sequences, in consideration of varying mutation rates across sites. We now report a further improvement of NG, LWL, MLWL, LPB, MLPB, and YN methods based on an introduction of gamma distribution to illustrate the variation of raw mutation rate over sites. The novelty comes in two ways: (1) we incorporate an optimal gamma distribution shape parameter a into gamma-NG, gamma-LWL, gamma-MLWL, gamma-LPB, gamma-MLPB, and gamma-YN methods; (2) we investigate how variable substitution rates affect the methods that adopt different models as well as the interplay among four evolutional features with respect to Ka/Ks computations. Our results suggest that variable substitution rates over sites under negative selection exhibit an opposite effect on omega estimates compared with those under positive selection. We believe that the sensitivity of our new methods has been improved than that of their original methods under diverse conditions and it is advantageous to introduce novel parameters for Ka/Ks computation.
authors: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
authors: Dapeng
authors: D
authors: Wang
authors: Song
authors: S
authors: Zhang
authors: Fuhong
authors: F
authors: He
authors: Jiang
authors: J
authors: Zhu
authors: Songnian
authors: S
authors: Hu
authors: Jun
authors: J
authors: Yu
mesh_terms: D000465:Algorithms; D019943:Amino Acid Substitution / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D019295:Computational Biology; D003198:Computer Simulation; D006801:Humans
chemical_list: D003062:Codon