Synonymous and non-synonymous transitions/transversions vividly disclose purifying selection in Escherichia coli coding sequences

Abstract

Transition (ti) and transversion (tv) are the major causes for genome variation. The accurate estimation of ti to tv ratio [Formula] in genomes is crucial for understanding of mutational and selection processes in organisms as it is influenced by both codon degeneracy and pretermination codons (PTC). Therefore, we developed a method (accessible at https://github.com/CBBILAB/CBBI.git) to estimate [Formula] ratio by accounting codon degeneracy as well as PTC in protein coding sequences. Our findings revealed a distinct impact of codon degeneracy and PTC on the [Formula] ratio in the Escherichia coli genome. We observed a decreasing order among the frequencies of different base substitutions such as synonymous transition (Sti) > synonymous transversion (Stv) > non-synonymous transition (Nti) > non-synonymous transversion (Ntv) in E. coli genome. The correlation was strong between Sti and Stv values (Pearson r value 0.795) whereas the correlation was weak between Sti and Nti (Pearson r value 0.192). Coding sequences with similar Sti values exhibited a wide range of Nti values. This indicated the varying strength of purifying selection acting on the coding sequences. In concordance with the assumption, the genes having higher Nti values were observed with lower codon adaptation index (CAI) values than that of the genes having lower Nti values. Our approach is convenient to visualize the frequency of base substitution variation as well as selection in protein coding sequences. The proposed method is useful to estimate different [Formula] ratios accurately in coding sequences and is insightful from an evolutionary perspective. Article SummaryGenetic diversity is pivotal in evolution, with base substitution as a key driver. Transition (ti) frequency surpasses transversion (tv) frequency in genomes, making [Formula] ratios a valuable metric for studying mutation bias. Our improved estimator for [Formula] calculation accounts for codon degeneracy and nonsense substitutions in pretermination codons. Additionally, we unveil insights into the frequency of different substitutions such as Sti, Stv, Nti, and Ntv and demonstrate the impact of selection on protein coding sequences.