Discovery of positive and purifying selection in metagenomic time series of hypermutator microbial populations

Maddamsetti, Rohan; Grant, Nkrumah A.

doi:10.1371/journal.pgen.1010324

Cited by 5 publications

(10 citation statements)

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“…When a solid line falls below the shaded region, then the gene set of interest shows a significant signal of purifying selection ( P < 0.025 for a one-tailed test for purifying selection). For further details, see figure 2 of Maddamsetti and Grant (2022) , which illustrates how STIMS works. ( A ) The result of running STIMS on enzymes in the BiGG E. coli core metabolism model.…”

Section: Resultsmentioning

confidence: 99%

“…Two non-mutator populations are significantly depleted of mutations in specialist enzymes ( supplementary fig. S2 A , Supplementary Material online): Ara+1 (STIMS bootstrap: P = 0.01) and Ara+2 (STIMS bootstrap: P = 0.035), although it is unclear whether the patterns in the non-mutator populations reflect relaxed or purifying selection ( Grant et al 2021b ; Maddamsetti and Grant 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…To test this hypothesis, we developed a randomization test that we call STIMS (Simple Test to Infer Mode of Selection) to detect selection on pre-defined sets of genes, using metagenomic time series covering 62,750 generations of the LTEE ( Good et al 2017 ). STIMS can detect positive as well as purifying selection in hypermutator populations, and is able to control for both temporal variation in mutation rates over time, as well as mutation rate variation over the chromosome ( Maddamsetti and Grant 2020 ; Maddamsetti and Grant 2022 ). Using STIMS, we found evidence of purifying selection on aerobic-specific and anaerobic-specific genes ( Grant et al 2021b ) and essential genes ( Maddamsetti and Grant 2022 ) in the LTEE.…”

Section: Introductionmentioning

confidence: 99%

“…STIMS can detect positive as well as purifying selection in hypermutator populations, and is able to control for both temporal variation in mutation rates over time, as well as mutation rate variation over the chromosome ( Maddamsetti and Grant 2020 ; Maddamsetti and Grant 2022 ). Using STIMS, we found evidence of purifying selection on aerobic-specific and anaerobic-specific genes ( Grant et al 2021b ) and essential genes ( Maddamsetti and Grant 2022 ) in the LTEE. In addition, we found evidence of purifying selection on protein interactome resilience ( Maddamsetti 2021a ), and purifying selection on genes encoding highly expressed and highly interacting proteins ( Maddamsetti 2021b ), using different methods.…”

Section: Introductionmentioning

confidence: 99%

“…Second, I hypothesized that specialist enzymes would show stronger purifying selection than generalist enzymes, because Nam et al (2012) reported that specialist enzymes are frequently essential and maintain higher metabolic flux than generalist enzymes. While this analysis focuses on the hypermutator LTEE populations due to substantially greater power to detect purifying selection ( Maddamsetti and Grant 2022 ), I also report the result of running STIMS on the non-mutator populations for the sake of completeness.…”

Section: Introductionmentioning

confidence: 99%

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Idiosyncratic Purifying Selection on Metabolic Enzymes in the Long-Term Evolution Experiment with Escherichia coli

Maddamsetti

2022

Genome Biology and Evolution

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Bacteria, Archaea, and Eukarya all share a common set of metabolic reactions. This implies that the function and topology of central metabolism has been evolving under purifying selection over deep time. Central metabolism may similarly evolve under purifying selection during long-term evolution experiments, although it is unclear how long such experiments would have to run (decades, centuries, millennia) before signs of purifying selection on metabolism appear. I hypothesized that central and superessential metabolic enzymes would show evidence of purifying selection in the long-term evolution experiment with Escherichia coli (LTEE). I also hypothesized that enzymes that specialize on single substrates would show stronger evidence of purifying selection in the LTEE than generalist enzymes that catalyze multiple reactions. I tested these hypotheses by analyzing metagenomic time series covering 62,750 generations of the LTEE. I find mixed support for these hypotheses, because the observed patterns of purifying selection are idiosyncratic and population-specific. To explain this finding, I propose the Jenga hypothesis, named after a children’s game in which blocks are removed from a tower until it falls. The Jenga hypothesis postulates that loss-of-function mutations degrade costly, redundant, and nonessential metabolic functions. Replicate populations can therefore follow idiosyncratic trajectories of lost redundancies, despite purifying selection on overall function. I tested the Jenga hypothesis by simulating the evolution of 1,000 minimal genomes under strong purifying selection. As predicted, the minimal genomes converge to different metabolic networks. Strikingly, the core genes common to all 1,000 minimal genomes show consistent signatures of purifying selection in the LTEE.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Idiosyncratic Purifying Selection on Metabolic Enzymes in the Long-Term Evolution Experiment with Escherichia coli

Maddamsetti

2022

Genome Biology and Evolution

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STEMSIM: a simulator of within-strain short-term evolutionary mutations for longitudinal metagenomic data

Zhou

2023

Bioinformatics

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Motivation As the resolution of metagenomic analysis increases, the evolution of microbial genomes in longitudinal metagenomic data has become a research focus. Some software has been developed for the simulation of complex microbial communities at the strain level. However, the tool for simulating within-strain evolutionary signals in longitudinal samples is still lacking. Results In this study, we introduce STEMSIM, a user-friendly command-line simulator of short-term evolutionary mutations for longitudinal metagenomic data. The input is simulated longitudinal raw sequencing reads of microbial communities or single species. The output is the modified reads with within-strain evolutionary mutations and the relevant information of these mutations. STEMSIM will be of great use for the evaluation of analytic tools that detect short-term evolutionary mutations in metagenomic data. Availability STEMSIM and its tutorial are freely available online at https://github.com/BoyanZhou/STEMSim. Supplementary information Supplementary data are available at Bioinformatics online.

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Idiosyncratic purifying selection on metabolic enzymes in the long-term evolution experiment withEscherichia coli

Maddamsetti

2021

Preprint

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Bacteria, Archaea, and Eukarya all share a common set of metabolic reactions. This implies that the function and topology of central metabolism has been evolving under purifying selection over deep time. Central metabolism may similarly evolve under purifying selection during longterm evolution experiments, although it is unclear how long such experiments would have to run (decades, centuries, millennia) before signs of purifying selection on metabolism appear. I hypothesized that central and superessential metabolic enzymes would show evidence of purifying selection in the long-term evolution experiment with Escherichia coli (LTEE), in which 12 initially identical bacterial populations have been evolving in the laboratory for more than 30 years and 60,000 bacterial generations. I also hypothesized that enzymes that specialize on single substrates would show stronger evidence of purifying selection in the LTEE than generalist enzymes that catalyze multiple reactions. I tested these hypotheses by analyzing metagenomic time series covering 60,000 generations of the LTEE. I find mixed support for these hypotheses: patterns of purifying selection on metabolic enzymes, at least after 60,000 generations of experimental evolution, are largely idiosyncratic and population-specific.Significance StatementPurifying selection conserves organismal function over evolutionary time. I looked for evidence of purifying selection on metabolic enzymes in an ongoing long-term evolution experiment with E. coli. While some populations show signs of purifying selection, the overall pattern is inconsistent. To explain this finding, I propose that each population’s metabolism is evolving in a molecular game of Jenga. In this conceptual model, loss-of-function mutations degrade costly, redundant, and inessential metabolic functions, after which purifying selection begins to dominate. The threshold at which purifying selection activates depends on the idiosyncratic trajectory of lost redundancies in each population.

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Discovery of positive and purifying selection in metagenomic time series of hypermutator microbial populations

Cited by 5 publications

References 67 publications

Idiosyncratic Purifying Selection on Metabolic Enzymes in the Long-Term Evolution Experiment with Escherichia coli

Idiosyncratic Purifying Selection on Metabolic Enzymes in the Long-Term Evolution Experiment with Escherichia coli

STEMSIM: a simulator of within-strain short-term evolutionary mutations for longitudinal metagenomic data

Idiosyncratic purifying selection on metabolic enzymes in the long-term evolution experiment withEscherichia coli

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