ZPS: visualization of recent adaptive evolution of proteins

Chattopadhyay, Sujay; Dykhuizen, Daniel E.; Sokurenko, Evgeni V.

doi:10.1186/1471-2105-8-187

Cited by 20 publications

(27 citation statements)

References 17 publications

(22 reference statements)

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“…To define whether or not the hot spot mutations were recent from evolutionary perspectives, we determined whether or not, respectively, their acquisition was followed by accumulation of synonymous changes in the corresponding alleles. This analysis was done by using the zonal phylogeny software tool (6,40). In both Salmonella and E. coli, the vast majority of hot spot mutations (in 85.4% and 89.3% of genes with hot spots, respectively) were of evolutionarily recent origin (Table 1), i.e., the pattern typical for pathoadaptive mutations in bacterial pathogens.…”

Section: Resultsmentioning

confidence: 99%

Convergent Molecular Evolution of Genomic Cores in Salmonella enterica and Escherichia coli

et al. 2012

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ABSTRACTOne of the strongest signals of adaptive molecular evolution of proteins is the occurrence of convergent hot spot mutations: repeated changes in the same amino acid positions. We performed a comparative genome-wide analysis of mutation-driven evolution of core (omnipresent) genes in 17 strains ofSalmonella entericasubspecies I and 22 strains ofEscherichia coli. More than 20% of core genes in bothSalmonellaandE. coliaccumulated hot spot mutations, with a predominance of identical changes having recent evolutionary origin. There is a significant overlap in the functional categories of the adaptively evolving genes in both species, although mostly via separate molecular mechanisms. As a strong evidence of the link between adaptive mutations and virulence inSalmonella, two human-restricted serovars, Typhi and Paratyphi A, shared the highest number of genes with serovar-specific hot spot mutations. Many of the core genes affected by Typhi/Paratyphi A-specific mutations have known virulence functions. For each species, a list of nonrecombinant core genes (and the hot spot mutations therein) under positive selection is provided.

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Section: Resultsmentioning

confidence: 99%

Convergent Molecular Evolution of Genomic Cores in Salmonella enterica and Escherichia coli

et al. 2012

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“…Zonal phylogeny analysis and associated statistics were carried out using Zonal Phylogeny software (ZPS), in which the corresponding protein tree is depicted from the DNA phylogram and the structural variants are classified as members of two zones: the primary zone, with multiallelic structural variants (the alleles of each variant being synonymously differentiated), representing the evolutionarily long-term category, and the external zone, with single-allele structural variants (where synonymous mutations have not yet accumulated within the variants), representing the evolutionarily short-term or recent category (46). Average pairwise nucleotide diversity () and the rates of synonymous (dS) and nonsynonymous (dN) mutations between and within the clades were calculated using MEGA4 program (47).…”

Section: Methodsmentioning

confidence: 99%

Structural and Population Characterization of MrkD, the Adhesive Subunit of Type 3 Fimbriae

et al. 2013

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Type 3 fimbriae are adhesive organelles found in enterobacterial pathogens. The fimbriae promote biofilm formation on biotic and abiotic surfaces; however, the exact identity of the receptor for the type 3 fimbriae adhesin, MrkD, remains elusive. We analyzed naturally occurring structural and functional variabilities of the MrkD adhesin from Klebsiella pneumoniae and Escherichia coli isolates of diverse origins. We identified a total of 33 allelic variants of mrkD among 90 K. pneumoniae isolates and 10 allelic variants among 608 E. coli isolates, encoding 11 and 9 protein variants, respectively. Based on the level of accumulated silent variability between the alleles, mrkD was acquired a relatively long time ago in K. pneumoniae but recently in E. coli. However, unlike K. pneumoniae, mrkD in E. coli is actively evolving under a strong positive selection by accumulation of mutations, often targeting the same positions in the protein. Several naturally occurring MrkD protein variants from E. coli were found to be significantly less adherent when tested in a mannan-binding assay and showed reduced biofilm-forming capacity. Functional examination of the MrkD adhesin in flow chamber experiments determined that it interacts with Saccharomyces cerevisiae cells in a shear-dependent manner, i.e., the binding is catch-bond-like and enhanced under increasing shear conditions. Homology modeling strongly suggested that MrkD has a two-domain structure, comprising a pilin domain anchoring the adhesin to the fimbrial shaft and a lectin domain containing the binding pocket; this is similar to structures found in other catch-bond-forming fimbrial adhesins in enterobacteria.

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“…In contrast, protein variants that have emerged only recently are likely to be encoded by single alleles, i.e., exhibiting no silent diversification among different strains. ZPS allows identification of long-term versus recent nonsynonymous variation in specific genes by collapsing silent changes along the DNA tree into corresponding protein variant nodes (23). On average, a core gene encoded 1.7 long-term and 3.7 recent protein variants ( Table 2).…”

Section: Clonalmentioning

confidence: 99%

“…S1). Because such substantial frequency of homoplasy suggests frequent occurrence of hotspot mutations, we investigated this possibility further using ZP software (ZPS) that is able to identify the number and nature of replacement hotspot mutations using protein trees reconstructed from the corresponding DNA trees (23).…”

Section: Clonalmentioning

confidence: 99%

“…We have recently developed a molecular evolution tool, zonal phylogeny (ZP) analysis, specifically designed to identify footprints of positive selection in genes with minimal changes per unique sequence variant (i.e., allele), by differentiating them from variations that are either selectively neutral or detrimental (21)(22)(23). Among several approaches used by ZP is the identification of replacement hotspot mutations-repeated, phylogenetically unlinked mutations in the same amino acid position.…”

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High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection

Chattopadhyay

Weissman²,

Minin

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Core genes comprising the ubiquitous backbone of bacterial genomes are not subject to frequent horizontal transfer and generally are not thought to contribute to the adaptive evolution of bacterial pathogens. We determined, however, that at least one-third and possibly more than one-half of the core genes in Escherichia coli genomes are targeted by repeated replacement substitutions in the same amino acid positions-hotspot mutations. Occurrence of hotspot mutations is driven by positive selection, as their rate is significantly higher than expected by random chance alone, and neither intragenic recombination nor increased mutability can explain the observed patterns. Also, commensal E. coli strains have a significantly lower frequency of mutated genes and mutations per genome than pathogenic strains. E. coli strains causing extra-intestinal infections accumulate hotspot mutations at the highest rate, whereas the highest total number of mutated genes has been found among Shigella isolates, suggesting the pathoadaptive nature of such mutations. The vast majority of hotspot mutations are of recent evolutionary origin, implying shortterm positive selection, where adaptive mutations emerge repeatedly but are not sustained in natural circulation for long. Such pattern of dynamics is consistent with source-sink model of virulence evolution.commensal ͉ E. coli core genome ͉ extra-intestinal ͉ pathoadaptive evolution ͉ Shigella

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ZPS: visualization of recent adaptive evolution of proteins

Cited by 20 publications

References 17 publications

Convergent Molecular Evolution of Genomic Cores in Salmonella enterica and Escherichia coli

Convergent Molecular Evolution of Genomic Cores in Salmonella enterica and Escherichia coli

Structural and Population Characterization of MrkD, the Adhesive Subunit of Type 3 Fimbriae

High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection

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