Transcribed intergenic regions exhibit a lower frequency of nucleotide polymorphism than the untranscribed intergenic regions in the genomes of Escherichia coli and Salmonella enterica

Abstract

The temporary exposure of single-stranded regions in the genome during the process of replication and transcription makes the region vulnerable to cytosine deamination resulting higher rate of C T transitions. Intra-operon intergenic regions undergo transcription along with adjacent co-transcribed genes in an operon, whereas inter-operon intergenic regions only undergo replication. Hence these two types of intergenic regions (IGRs) can be compared to find out the contribution of replication-associated mutations (RAM) and transcriptionassociated mutations (TrAM) towards bringing variation in genomes. In our work, we performed a polymorphism spectra comparison between intra-operon IGRs and inter-operon IGRs in genomes of two well-known closely related bacteria such as Escherichia coli and Salmonella enterica. In general, the size of intra-operon IGRs was smaller than that of interoperon IGRs in these bacteria. Interestingly, the polymorphism frequency at intra-operon IGRs was 2.5-fold lesser than that in the inter-operon IGRs in E. coli genome. Similarly, the polymorphism frequency at intra-operon IGRs was 2.8-fold lesser than that in the inter-operon IGRs in S. enterica genome. Therefore, the intra-operon IGRs were often observed to be more conserved. In the case of inter-operon IGRs, the T C transition frequency was a minimum of two times more than T A transversion frequency whereas in the case of intra-operon IGRs, T C transition frequency was similar to that of T A transversion frequency. The polymorphism was purine biased and keto biased more in intra-operon IGRs than the interoperon IGRs. In E. coli, the Ti/Tv ratio was observed as 1.639 and 1.338 in inter-operon and in intra-operon IGRs, respectively. In S. enterica, the Ti/Tv ratio was observed as 2.134 and 2.780 in inter-operon and in intra-operon IGRs, respectively. The observation in this study indicates that transcribed IGRs might not always have higher polymorphism frequency than the untranscribed IGRs. The lower polymorphism frequency at intra-operon IGRs might be attributed to different events such as the transcription-coupled DNA repair, sequences facilitating translation initiation and avoidance of rho-dependent transcription termination.

Synonymous and non-synonymous transitions/transversions vividly disclose purifying selection inEscherichia colicoding sequences

“…Susceptibility of different sites for ti and tv are not same as evident by C→T ti and G→T tv are more frequent than the other ti and tv , respectively (Sen et al . 2022; Beura et al . 2023).…”

“…The logic is that the most abundant nucleotide in a species is the ancestral nucleotide in the species (Sen et al 2022; Aziz et al . 2022; Sen 2022, Beura et al . 2023).…”

“…The logic behind the derivation of the reference sequence is that the most abundant nucleotide in a position is considered as the ancestral nucleotide for the position (Sen et al 2022; Aziz et al . 2022; Sen 2022, Beura et al . 2023).…”

“…In case of improved Sti and improved Stv cases the possible sites have been normalized respectively. Susceptibility of different sites for ti and tv are not same as evident by C T ti and G T tv are more frequent than the other ti and tv, respectively(Sen et al 2022;Beura et al 2023). Therefore, the correlation value between improved Sti and improved Stv is likely to be weaker than the same between Sti and Stv values.As transitions are more frequent events than transversion, transition can be consideredalone to understand the selection on coding sequences.…”

“…Accordingly, it has been recently reported that the synonymous variation in TFD codons is relatively higher than the FFD codons in Escherichia coli (Aziz et al 2022). Therefore, in any organism, the ratio is likely to vary across the coding sequences having differences in degenerate codon composition (Beura et al 2023). Hence, an estimation of ௧ ௧௩ ratio in a coding sequence by accounting codon degeneracy and PTC compositions will be important to further carrying out comparative analysis of this value among coding sequences in a genome.…”