A selective force favoring increased G+C content in bacterial genes

Raghavan, Rahul; Kelkar, Yogeshwar D.; Ochman, Howard

doi:10.1073/pnas.1205683109

Cited by 119 publications

(147 citation statements)

References 33 publications

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“…= 1, P = 0.27) ( Table 2). Thus, indels in B. cenocepacia are expected to reduce genome wide %GC content, further supporting the need for other population-genetic processes to account for the composition of high-GC genomes (Lynch et al 2008;Duret and Galtier 2009;Raghavan et al 2012;Zhu et al 2014;Lassalle et al 2015). Overall, the observed mutation spectra in this study suggest that the natural indel spectrum of B. cenocepacia causes both genome-size reduction and increased %AT content.…”

Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 53%

“…A universal mutation bias in the direction of AT has been observed in all other wild-type species studied by MA (Table 1) and has also been inferred in comparative analyses of several bacterial species, including B. pseudomallei (Lynch et al 2008;Denver et al 2009Denver et al , 2012Keightley et al 2009;Hershberg and Petrov 2010;Hildebrand et al 2010;Lynch 2010a;Ossowski et al 2010;Sung et al 2012a, b;Lee et al 2012;Schrider et al 2013;Zhu et al 2014). Thus, biased gene conversion and selection have been invoked to explain the high %GC content realized in many genomes (Lynch et al 2008;Duret and Galtier 2009;Raghavan et al 2012;Zhu et al 2014;Lassalle et al 2015). Our data for B. cenocepacia are inconsistent with prior published studies showing a mutation bias in the direction of AT (Table 1), but also suggest that biased gene conversion and/or selection must have mostly generated the realized %GC content of B. cenocepacia, which is substantially higher than expected based on mutation pressure alone.…”

Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 97%

“…G:C transitions are nearly indistinguishable at six of the seven loci (see Figure S7). However, the evolutionary mechanism of these substitution biases are uncertain, given the potential for ongoing recombination and/or natural selection to influence polymorphisms at these sites in conserved housekeeping genes (Lynch et al 2008;Duret and Galtier 2009;Raghavan et al 2012;Zhu et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, although mutation pressure in B. cenocepacia does not favor AT bases, it is clear that the observed mutation bias is not sufficient to elicit the realized %GC content of 66.8%. Thus, either the B. cenocepacia genome is still moving toward mutation-drift equilibrium, or GC-biased gene conversion and/or natural selection are responsible for the observed %GC content (Lynch et al 2008;Duret and Galtier 2009;Raghavan et al 2012;Zhu et al 2014;Lassalle et al 2015).…”

Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 99%

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The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia

et al. 2015

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Spontaneous mutations are ultimately essential for evolutionary change and are also the root cause of many diseases. However, until recently, both biological and technical barriers have prevented detailed analyses of mutation profiles, constraining our understanding of the mutation process to a few model organisms and leaving major gaps in our understanding of the role of genome content and structure on mutation. Here, we present a genome-wide view of the molecular mutation spectrum in Burkholderia cenocepacia, a clinically relevant pathogen with high %GC content and multiple chromosomes. We find that B. cenocepacia has low genome-wide mutation rates with insertion-deletion mutations biased toward deletions, consistent with the idea that deletion pressure reduces prokaryotic genome sizes. Unlike prior studies of other organisms, mutations in B. cenocepacia are not AT biased, which suggests that at least some genomes with high %GC content experience unusual base-substitution mutation pressure. Importantly, we also observe variation in both the rates and spectra of mutations among chromosomes and elevated G:C . T:A transversions in late-replicating regions. Thus, although some patterns of mutation appear to be highly conserved across cellular life, others vary between species and even between chromosomes of the same species, potentially influencing the evolution of nucleotide composition and genome architecture.KEYWORDS mutation rate; genome evolution; replication timing; mutation spectra A S the ultimate source of genetic variation, mutation is implicit in every aspect of genetics and evolution. However, as a result of the genetic burden imposed by deleterious mutations, remarkably low mutation rates have evolved across all of life, making detection of these rare events technologically challenging and accurate measures of mutation rates and spectra exceedingly difficult (Kibota and Lynch 1996;Lynch and Walsh 1998;Sniegowski et al. 2000;Lynch 2011;Fijalkowska et al. 2012;Zhu et al. 2014). Until recently, most estimates of mutational properties have been derived indirectly using comparative genomics at putatively neutral sites (Graur and Li 2000;Wielgoss et al. 2011) or by extrapolation from small reporter-construct studies (Drake 1991). Both of these methods are subject to potentially significant biases, as many putatively neutral sites are subject to selection and mutation rates can vary substantially among different genomic regions (Lynch 2007).To avoid the potential biases of these earlier methods, pairing classic mutation accumulation (MA) with wholegenome sequencing (WGS) has become the preferred method for obtaining direct measures of mutation rates and spectra (Lynch et al. 2008;Denver et al. 2009;Ossowski et al. 2010;Lee et al. 2012; Sung et al. 2012a,b;Heilbron et al. 2014). Using this strategy, a single clonal ancestor is used to initiate several replicate lineages that are subsequently passaged through repeated single-cell bottlenecks for several thousand generations. The complete genomes of ea...

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Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 53%

Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Base-substitution Mutations Are Not At Biasedmentioning

confidence: 99%

See 2 more Smart Citations

The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia

et al. 2015

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“…This finding provides further evidence that differences in amino acid utilization between SAGs and cultures are driven primarily by differences in %GC. Recent experimental work suggests that high GC content may enhance bacterial growth in laboratory conditions (26). In contrast, low genomic GC content may be an adaptation to nitrogen limitation (27) or a result of mutational biases in the absence of effective DNA repair systems (16).…”

Section: Resultsmentioning

confidence: 99%

Prevalent genome streamlining and latitudinal divergence of planktonic bacteria in the surface ocean

Swan

Tupper

Sczyrba

et al. 2013

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

331

319

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Planktonic bacteria dominate surface ocean biomass and influence global biogeochemical processes, but remain poorly characterized owing to difficulties in cultivation. Using large-scale single cell genomics, we obtained insight into the genome content and biogeography of many bacterial lineages inhabiting the surface ocean. We found that, compared with existing cultures, natural bacterioplankton have smaller genomes, fewer gene duplications, and are depleted in guanine and cytosine, noncoding nucleotides, and genes encoding transcription, signal transduction, and noncytoplasmic proteins. These findings provide strong evidence that genome streamlining and oligotrophy are prevalent features among diverse, freeliving bacterioplankton, whereas existing laboratory cultures consist primarily of copiotrophs. The apparent ubiquity of metabolic specialization and mixotrophy, as predicted from single cell genomes, also may contribute to the difficulty in bacterioplankton cultivation. Using metagenome fragment recruitment against single cell genomes, we show that the global distribution of surface ocean bacterioplankton correlates with temperature and latitude and is not limited by dispersal at the time scales required for nucleotide substitution to exceed the current operational definition of bacterial species. Single cell genomes with highly similar small subunit rRNA gene sequences exhibited significant genomic and biogeographic variability, highlighting challenges in the interpretation of individual gene surveys and metagenome assemblies in environmental microbiology. Our study demonstrates the utility of single cell genomics for gaining an improved understanding of the composition and dynamics of natural microbial assemblages.comparative genomics | marine microbiology | microbial ecology | microbial microevolution | operational taxonomic unit

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Base-Biased Evolution of Disease-Associated Mutations in the Human Genome

Cheng

Chen

2016

Human Mutation

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Understanding the evolution of disease-associated mutations is fundamental to analyze pathogenetics of diseases. Mutation, recombination (by GC-biased gene conversion, gBGC), and selection have been known to shape the evolution of disease-associated mutations, but how these evolutionary forces work together is still an open question. In this study, we analyzed several human large-scale datasets (1000 Genomes, ESP6500, ExAC and ClinVar), and found that base-biased mutagenesis generates more GC→AT than AT→GC mutations, while gBGC promotes the fixation of AT→GC mutations to balance the impact of base-biased mutation on genome. Due to this effect of gBGC, purifying selection removes more deleterious AT→GC mutations than GC→AT from population, but many high-frequency (fixed and nearly fixed) deleterious AT→GC mutations are remained possibly due to high genetic load. As a special subset, disease-associated mutations follow this evolutionary rule, in which disease-associated GC→AT mutations are more enriched in rare mutations compared with AT→GC, while disease-associated AT→GC are more enriched in mutations with high frequency. Thus, we presented a base-biased evolutionary framework that explains the base-biased generation and accumulation of disease-associated mutations in human populations.

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A selective force favoring increased G+C content in bacterial genes

Cited by 119 publications

References 33 publications

The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia

The Rate and Molecular Spectrum of Spontaneous Mutations in the GC-Rich Multichromosome Genome of Burkholderia cenocepacia

Prevalent genome streamlining and latitudinal divergence of planktonic bacteria in the surface ocean

Base-Biased Evolution of Disease-Associated Mutations in the Human Genome

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