Biology subjects

Aziz, R.

Publications and source records attributed to Aziz, R..

8 recordsLinked to original sources

bioRxiv2026

Expression-dependent but strand-independent synonymous single-nucleotide polymorphism in the Escherichia coli chromosome

AbstractMutation in genomes is mainly attributed to replication, though transcription is also known to be mutagenic and is a more frequent event than replication in an organism. Recently, there have been reports regarding genome-wide transcription-induced mutagenesis. However, a distinct demonstration of specific mutation being replication-dependent and/or transcription-dependent in genomes is yet to be established. Here, we studied synonymous single-nucleotide polymorphisms (SNPs) in 2091 individual coding sequences (CDS) in the leading strand (LeS) and the lagging strand (LaS) of the Escherichia coli chromosome by comparing across 157 strains. The frequencies of complementary transitions (ti) and complementary transversions (tv) were compared in each CDS to assess parity violation in the context of strand location and gene expression. The C[->]T and G[->]A exhibited the maximum frequency as well as the most prominent strand inequality as these tis were influenced both by the strand location as well as by the gene expression. Interestingly, inequality between T[->]C and A[->]G was expression-dependent but strand-independent. This was a direct demonstration of strand inequality due to expression but not due to replication. A[->]T and G[->]T tvs were universally more frequent than their complementary T[->]A and C[->]A, respectively. The strand-independent but expression-dependent synonymous SNP inequality in CDS, supports the role of transcription-induced mutagenesis contributing to strand inequality in the E. coli chromosome. Significance StatementMutational patterns in bacterial genomes are shaped by both replication and transcription, but their relative roles remain unclear. By analyzing synonymous SNPs across 157 strains of E. coli, we identify strong strand-specific asymmetry consistent with replication-associated biases. A strong asymmetry between the strands regarding C[->]T and G[->]A ti is observed, as it is influenced by replication asymmetry and expression. We further show that gene expression significantly influences mutation types, with T[->]C ti being enriched in the highly expressed genes and A[->]G ti being enriched in the lowly expressed genes. Notably, A[->]T ti is strand independent but exhibits mild dependency on gene expression, revealing a previously unrecognized mutational pattern. These findings highlight how some SNPs are influenced by transcription but not replication

evolutionary biology↗

bioRxiv2022

Codon degeneracy as well as pretermination codons influence transition to transversion ratio in coding sequences

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.

evolutionary biology↗

bioRxiv2022

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

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 transcription-associated 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 inter-operon 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 inter-operon 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.

evolutionary biology↗

bioRxiv2022

Synonymous polymorphism difference relating to codon degeneracy between co-transcribed genes in the genome of Escherichia coli

The previous findings suggest that replication and transcription are two major reasons behind the different substitution patterns of mutations in genomic DNA. In the current work, we have compared the adjacent co-transcribed gene pairs regarding synonymous polymorphism in five different operons in Escherichia coli. It is interesting that the co-transcribed genes were different from each other regarding the polymorphism spectra. The transition to transversion ratio between gene pairs were different due to their compositional differences regarding two-fold degenerate codon and four-fold degenerate codons. Further, the polymorphism spectra difference between the gene pairs was more prominent in four-fold and six-fold degenerate codons than in the two-fold degenerate codons. In case of rpoB and rpoC, the major difference was found at UCC, GUA, CCG, GCU, GGC and CGC codons. Similarly, in case of the other four pairs of co-transcribed genes, the difference was more prominent in the higher degenerate codons than the two-fold degenerate codons. It may be that the restriction of two-fold degenerate codons to transition substitutions only regarding synonymous polymorphism is making these codons different from the higher degeneracy codons in this study.

evolutionary biology↗

bioRxiv2022

Modified dN/dS for accounting transition and transversion frequency difference and non-sense substitution in genomes

The dN/dS value is estimated in homologous protein coding gene sequences between two closely related organisms for studying selection on the genes. In the usual method of calculation of synonymous (S) and non-synonymous (NS) sites in codons, the transition and transversion rates are considered same as well as no difference of pretermination codons from the other codons regarding NS substitutions is considered. In this study we are proposing a modification in the method by estimating the S and the NS sites in codons by considering difference between the transition and transversion rates and the NS substitutions leading to non-sense codons in pretermination codons. So, the dN/dS value calculated by our approach was higher than that calculated by the earlier method. The modified method was applied in estimating dN/dS in 29 homologous gene sequences of Escherichia coli and Salmonella enterica. Impact of codon degeneracy and pretermination codons on the dN/dS values estimated by our method were observed clearly. Our method of estimation that considers the above features is a realistic representation of dN/dS values in coding sequences.

evolutionary biology↗

bioRxiv2021

Polymorphism at four-fold degenerate site, but not at the intergenic regions, explains nucleotide compositional strand asymmetry in bacteria

We investigated single nucleotide polymorphism in intergenic regions (IRs) and four-fold degenerate sites (FFS) in genomes of three {gamma}-Proteobacteria and two Firmicutes to understand the mechanism of nucleotide compositional asymmetry between the leading and the lagging strands. Pattern of the polymorphism spectra were alike regarding transitions but variable regarding transversions in the IRs of these bacteria. Contrasting trends of complementary polymorphisms such as C[->]T vs G[->]A as well as A[->]G vs T[->]C in the IRs vindicated similar replication-associated strand asymmetry regarding cytosine and adenine deamination, respectively, across these bacteria. Surprisingly, the polymorphism pattern at FFS was different from that of the IRs and its frequency was always more than the IRs in these bacteria. Further, the polymorphism patterns within a bacterium were inconsistent across the five amino acids, which neither the replication nor the transcription-associated mutations could explain. However, the polymorphism at FFS coincided with amino acid specific codon usage bias in the five bacteria. Further, strand asymmetry in nucleotide composition could be explained by the polymorphism at FFS, not at the IRs. Therefore, polymorphisms at FFS might not be treated as nearly neutral unlike that in IRs in these bacteria.

molecular biology↗

bioRxiv2020

Validity of the Lumen(R) hand-held metabolic device to measure fuel utilization in healthy young adults

BackgroundMetabolic carts measure the carbon dioxide produced and oxygen consumed from the breath in order to assess metabolic fuel usage (carbohydrates vs. fats). However, these systems are expensive, time-consuming, and only available in the clinic. A small hand-held device capable of measuring metabolic fuel via CO2 from exhaled air has been developed ObjectiveTo evaluate the validity of a novel hand-held device (Lumen(R)) for measuring metabolic fuel utilization in healthy young adults MethodsMetabolic fuel usage was assessed in healthy participants (n = 33; age: 23.1 {+/-} 3.9 y) via respiratory exchange ratio (RER) values from the "gold-standard" metabolic cart as well as %CO2 from the Lumen device. Measurements were performed at rest in two conditions, fasting, and after consuming 150 grams of glucose in order to determine changes in metabolic fuel. Reduced major axis regression was performed as well as Bland-Altman plots and linear regressions to test for agreement between RER and Lumen %CO2. ResultsBoth RER and Lumen %CO2 significantly increased after glucose intake compared with fasting conditions (P < .0001). Regression analyses and Bland-Altman plots revealed an agreement between the two measurements with a systematic bias resulting from the nature of the different units. ConclusionsThis study shows the validity of Lumen(R) to estimate metabolic fuel utilization in a comparable manner with the "gold-standard" metabolic cart, providing the ability for real-time metabolic information for users under any circumstances.

physiology↗

bioRxiv2019

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the worlds countries, and showed that its phylogeography is locally clustered within countries, cities, and individuals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.

microbiology↗