A Study of the Middle-scale Nucleotide Clustering in DNA Sequences of Various Origin and Functionality, by means of a Method based on a Modified Standard Deviation

Nikolaou, Christoforos; Almirantis, Yannis

doi:10.1006/jtbi.2002.3045

Cited by 10 publications

(10 citation statements)

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“…DNA sequences of different functional types have been found to show compositional similarity across many genomes (Blaisdell et al 1986; Pietrokovski et al 1990; Nikolaou and Almirantis 2002). To assess whether the distinguishability of a fragment correlates with the function of any encoded genes, we examined a subset of between-genome comparisons for further analysis, including several outliers as well as comparisons at various CA levels with low residuals (supplementary table S2, Supplementary Material online).…”

Section: Resultsmentioning

confidence: 99%

Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

Perry

Beiko

2010

Genome Biology and Evolution

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It is well known that patterns of nucleotide composition vary within and among genomes, although the reasons why these variations exist are not completely understood. Between-genome compositional variation has been exploited to assign environmental shotgun sequences to their most likely originating genomes, whereas within-genome variation has been used to identify recently acquired genetic material such as pathogenicity islands. Recent sequence assignment techniques have achieved high levels of accuracy on artificial data sets, but the relative difficulty of distinguishing lineages with varying degrees of relatedness, and different types of genomic sequence, has not been examined in depth. We investigated the compositional differences in a set of 774 sequenced microbial genomes, finding rapid divergence among closely related genomes, but also convergence of compositional patterns among genomes with similar habitats. Support vector machines were then used to distinguish all pairs of genomes based on genome fragments 500 nucleotides in length. The nearly 300,000 accuracy scores obtained from these trials were used to construct general models of distinguishability versus taxonomic and compositional indices of genomic divergence. Unusual genome pairs were evident from their large residuals relative to the fitted model, and we identified several factors including genome reduction, putative lateral genetic transfer, and habitat convergence that influence the distinguishability of genomes. The positional, compositional, and functional context of a fragment within a genome has a strong influence on its likelihood of correct classification, but in a way that depends on the taxonomic and ecological similarity of the comparator genome.

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Section: Resultsmentioning

confidence: 99%

Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

Perry

Beiko

2010

Genome Biology and Evolution

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“…R. conorii and R. prowazekii are estimated to have diverged from a common ancestor 80 million years ago (42), and it would seem probable that sequences which were not under selection pressure during this period would have been more variable than coding sequences. For prokaryotes, variations in the conservation of spacers has been reported, but the role of conserved spacers is incompletely understood (39,44). For eukaryotes, recent studies on comparative genomics have shown that in yeasts (29) and mammals (11) some intergenic spacers are highly conserved at the species level.…”

Section: Discussionmentioning

confidence: 99%

Use of Highly Variable Intergenic Spacer Sequences for Multispacer Typing ofRickettsia conoriiStrains

et al. 2004

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By use of the nearly perfectly colinear genomes of Rickettsia conorii and Rickettsia prowazekii, we compared the usefulness of three types of sequences for typing of R. conorii isolates: (i) 5 variable coding genes comprising the 16S ribosomal DNA, gltA, ompB, and sca4 (gene D) genes, which are present in both genomes, and the ompA gene, which is degraded in R. prowazekii; (ii) 28 genes degraded in R. conorii but intact in R. prowazekii, including 23 split and 5 remnant genes; and (iii) 27 conserved and 25 variable intergenic spacers. The 4 conserved and 23 split genes as well as the 27 conserved intergenic spacers each had identical sequences in 34 human and 5 tick isolates of R. conorii. Analysis of the ompA sequences identified three genotypes of R. conorii. The variable intergenic spacers were significantly more variable than conserved genes, split genes, remnant genes, and conserved spacers (P < 10(-2) in all cases). Four of the variable intergenic spacers (dksA-xerC, mppA-purC, rpmE-tRNA(fMet), and tRNA(Gly)-tRNA(Tyr)) had highly variable sequences; when they were combined for typing, multispacer typing (MST) identified 27 different genotypes in the 39 R. conorii isolates. Two batches from the same R. conorii strain, Malish (Seven), with different culture passage histories were found to exhibit the same MST type. MST was more discriminatory for strain genotyping than multiple gene sequencing (P < 10(-2)). Phylogenetic analysis based on MST sequences was concordant with the geographic origins of R. conorii isolates. Our study supports the usefulness of MST for strain genotyping. This tool may be useful for tracing a strain and identifying its source during outbreaks, including those resulting from bioterrorism.

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“…It was demonstrated that X -rich MRI regions are highly overrepresented in mammalian genomes for all kinds X -contexts. Particular properties of MRI have also been investigated previously by Mrazek and Kypr [12] and also by Nikolaou and Almirantis [13]. This paper studies the effect of mutations on the evolution of MRI regions in primates.…”

Section: Introductionmentioning

confidence: 81%

Evolution of genomic sequence inhomogeneity at mid-range scales

Prakash

Shepard

et al. 2009

BMC Genomics

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BackgroundMid-range inhomogeneity or MRI is the significant enrichment of particular nucleotides in genomic sequences extending from 30 up to several thousands of nucleotides. The best-known manifestation of MRI is CpG islands representing CG-rich regions. Recently it was demonstrated that MRI could be observed not only for G+C content but also for all other nucleotide pairings (e.g. A+G and G+T) as well as for individual bases. Various types of MRI regions are 4-20 times enriched in mammalian genomes compared to their occurrences in random models.ResultsThis paper explores how different types of mutations change MRI regions. Human, chimpanzee and Macaca mulatta genomes were aligned to study the projected effects of substitutions and indels on human sequence evolution within both MRI regions and control regions of average nucleotide composition. Over 18.8 million fixed point substitutions, 3.9 million SNPs, and indels spanning 6.9 Mb were procured and evaluated in human. They include 1.8 Mb substitutions and 1.9 Mb indels within MRI regions. Ancestral and mutant (derived) alleles for substitutions have been determined. Substitutions were grouped according to their fixation within human populations: fixed substitutions (from the human-chimp-macaca alignment), major SNPs (> 80% mutant allele frequency within humans), medium SNPs (20% - 80% mutant allele frequency), minor SNPs (3% - 20%), and rare SNPs (<3%). Data on short (< 3 bp) and medium-length (3 - 50 bp) insertions and deletions within MRI regions and appropriate control regions were analyzed for the effect of indels on the expansion or diminution of such regions as well as on changing nucleotide composition.ConclusionMRI regions have comparable levels of de novo mutations to the control genomic sequences with average base composition. De novo substitutions rapidly erode MRI regions, bringing their nucleotide composition toward genome-average levels. However, those substitutions that favor the maintenance of MRI properties have a higher chance to spread through the entire population. Indels have a clear tendency to maintain MRI features yet they have a smaller impact than substitutions. All in all, the observed fixation bias for mutations helps to preserve MRI regions during evolution.

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A Study of the Middle-scale Nucleotide Clustering in DNA Sequences of Various Origin and Functionality, by means of a Method based on a Modified Standard Deviation

Cited by 10 publications

References 48 publications

Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

Use of Highly Variable Intergenic Spacer Sequences for Multispacer Typing ofRickettsia conoriiStrains

Evolution of genomic sequence inhomogeneity at mid-range scales

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