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

Dillon, Marcus M.; Sung, Way; Lynch, Michael; Cooper, Vaughn S.

doi:10.1534/genetics.115.176834

Cited by 74 publications

(106 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using this data set, we estimate a bpsm rate of 0.001 (6.02 3 10 25 )/genome/generation, an indel rate of 0.0002 (2.62 3 10 25 ) /genome/generation, and a rate of plasmid loss of 1.67 3 10 25 (8.17 3 10 26 )/genome/generation (SEM). which are similar to the rates that we reported previously but reflect the differences in our data sets described above (Dillon et al 2015).Among the 43 MA lineages, 233 bpsms, 42 short indels, and four plasmid loss events were identified. The most common class of bpsms was missense bpsms (141), followed by synonymous bpsms (49), intergenic bpsms (37), and nonsense bpsms (6).…”

supporting

confidence: 90%

“…MA studies have been used to characterize the fitness effects of spontaneous mutations in Drosophila melanogaster (Bateman 1959;Mukai 1964;Keightley 1994;Fry et al 1999) A more powerful approach for studying the fitness effects of spontaneous mutations is to pair MA experiments with wholegenome sequencing (MA-WGS), so that both the genetic basis and fitness effects of a collection of mutations can be known. MA-WGS studies have been conducted in a diverse array of bacteria, generating a growing database of naturally accumulated mutations that has dramatically improved estimates of mutation rates and spectra (Lee et al 2012;Sung et al 2012Sung et al , 2015Heilbron et al 2014;Long et al 2014Long et al , 2015Dillon et al 2015;Foster et al 2015;Dettman et al 2016). Yet, only one of these studies has also characterized the fitness of MA-WGS lines (Heilbron et al 2014), and this study was conducted with mutator lineages, which have altered base substitution and indel biases and produce hundreds of mutations per line (Lee et al 2012;Sung et al 2015).…”

mentioning

confidence: 99%

“…In any event, we estimate that the threshold selection coefficient below which genetic drift will overpower natural selection, as determined by N E 3 s ¼ 1 in haploid organisms, is 0.08 (Dillon et al 2015). Thus, while a small class of adaptive or deleterious mutations with effects in excess of s = 0.08 will be subject to the biases of natural selection (Kimura 1983;Elena et al 1998;Zeyl and de Visser 2001;Hall et al 2008), the vast majority of mutations that were observed in this study are likely fixed irrespective of their fitness effects. …”

mentioning

confidence: 99%

See 2 more Smart Citations

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

Dillon

Cooper

2016

Genetics

Self Cite

View full text Add to dashboard Cite

Mutation accumulation (MA) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. Thus, most mutations fix within MA lines independently of their fitness effects. This approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. However, a quantitative understanding of the fitness effects of mutations virtually unseen by selection has remained an untapped opportunity. Here, we analyzed the fitness of 43 sequenced MA lines of the multi-chromosome bacterium Burkholderia cenocepacia that had each undergone 5554 generations of MA and accumulated an average of 6.73 spontaneous mutations. Most lineages exhibited either neutral or deleterious fitness in three different environments in comparison with their common ancestor. The only mutational class that was significantly overrepresented in lineages with reduced fitness was the loss of the plasmid, though nonsense mutations, missense mutations, and coding insertion-deletions were also overrepresented in MA lineages whose fitness had significantly declined. Although the overall distribution of fitness effects was similar between the three environments, the magnitude and even the sign of the fitness of a number of lineages changed with the environment, demonstrating that the fitness of some genotypes was environmentally dependent. These results present an unprecedented picture of the fitness effects of spontaneous mutations in a bacterium with multiple chromosomes and provide greater quantitative support for the theory that the vast majority of spontaneous mutations are neutral or deleterious.KEYWORDS fitness effects; deleterious mutation; pleiotropy; genetic drift; Burkholderia cenocepacia T HE extent to which spontaneous mutations contribute to evolutionary change largely depends on their rates and fitness effects. Both parameters are fundamental to several evolutionary problems, including the maintenance of genetic variation (Charlesworth et al. 1993(Charlesworth et al. , 2009Charlesworth and Charlesworth 1998), the evolution of recombination (Muller 1964;Kondrashov 1988;Otto and Lenormand 2002;Roze and Blanckaert 2014), the evolution of mutator alleles (Sniegowski et al. 1997;Tenaillon et al. 1999), and deleterious mutation accumulation (MA) in small populations (Lande 1994;Lynch et al. 1995Lynch et al. , 1999Schwander and Crespi 2009). Many studies have now obtained direct and robust estimates of mutation rates and spectra across diverse organisms, but our understanding of the fitness effects of spontaneous mutations remains limited to mostly indirect estimates in classic model organisms (Eyre-Walker and Keightley 2007).MA experiments provide the opportunity to quantify properties of the fitness of spontaneous mutations that have not been exposed to the sieve of natural selection. Specifically, MA experiments limit the efficiency of natural selection by passaging replicate lineages throu...

show abstract

supporting

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

Dillon

Cooper

2016

Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…This lack of deviation from average GC% suggests instead that substitutions are not biased toward A+T in Burkholderia leaf nodule symbionts. This interpretation is supported by experimental data demonstrating an unusual mutational bias toward G+C in other Burkholderia species (Dillon et al, 2015).…”

Section: Horizontal Gene Transfer Between Obligate Leaf Nodule Symbiosupporting

confidence: 62%

Evidence of horizontal gene transfer between obligate leaf nodule symbionts

Pinto‐Carbó¹,

Sieber²,

Dessein³

et al. 2016

The ISME Journal

105

View full text Add to dashboard Cite

Bacteria of the genus Burkholderia establish an obligate symbiosis with plant species of the Rubiaceae and Primulaceae families. The bacteria, housed within the leaves, are transmitted hereditarily and have not yet been cultured. We have sequenced and compared the genomes of eight bacterial leaf nodule symbionts of the Rubiaceae plant family. All of the genomes exhibit features consistent with genome erosion. Genes potentially involved in the biosynthesis of kirkamide, an insecticidal C7N aminocyclitol, are conserved in most Rubiaceae symbionts. However, some have partially lost the kirkamide pathway due to genome erosion and are unable to synthesize the compound. Kirkamide synthesis is therefore not responsible for the obligate nature of the symbiosis. More importantly, we find evidence of intra-clade horizontal gene transfer (HGT) events affecting genes of the secondary metabolism. This indicates that substantial gene flow can occur at the early stages following host restriction in leaf nodule symbioses. We propose that host-switching events and plasmid conjugative transfers could have promoted these HGTs. This genomic analysis of leaf nodule symbionts gives, for the first time, new insights in the genome evolution of obligate symbionts in their early stages of the association with plants.

show abstract

“…Longterm mutation accumulation studies showed that B. cenocepacia has low genome-wide mutation rates, with many of the mutations biased toward deletions (Dillon et al 2015). Longitudinal sampling spanning up to 10 yr allowed us to ask if genome reduction occurs during the adaption of B. cenocepacia in CF patients.…”

Section: Recurrent Genomic Changes In B Cenocepacia During Long-termmentioning

confidence: 99%

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

et al. 2017

View full text Add to dashboard Cite

Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2-20 yr and a broad range of epidemic lineages. Systematic phenotypic tests identified longitudinal bacterial series that manifested progressive changes in liquid media growth, motility, biofilm formation, and acute insect virulence, but not in mucoidy. The results suggest that distinct lineages follow distinct evolutionary trajectories during lung infection. Pan-genome analysis identified 10,110 homologous gene clusters present only in a subset of strains, including genes restricted to different molecular types. Our phylogenetic analysis based on 2148 orthologous gene clusters from all isolates is consistent with patient-specific clades. This suggests that initial colonization of patients was likely by individual strains, followed by subsequent diversification. Evidence of clonal lineages shared by some patients was observed, suggesting inter-patient transmission. We observed recurrent gene losses in multiple independent longitudinal series, including complete loss of Chromosome III and deletions on other chromosomes. Recurrently observed loss-of-function mutations were associated with decreases in motility and biofilm formation. Together, our study provides the first comprehensive genome-phenome analyses of B. cenocepacia infection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution.

show abstract

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

Cited by 74 publications

References 74 publications

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

Evidence of horizontal gene transfer between obligate leaf nodule symbionts

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs

Contact Info

Product

Resources

About