2021
Maddamsetti R
Selection Maintains Protein Interactome Resilience in the Long-Term Evolution Experiment with Escherichia coli Journal Article
Genome Biology and Evolution, 13 (6), 2021.
Abstract | Links | BibTeX | Altmetric | Tags: Genome Evolution, Genotypes and Phenotypes
@article{Maddamsetti2021,
title = {Selection Maintains Protein Interactome Resilience in the Long-Term Evolution Experiment with \emph{Escherichia coli}},
author = {Rohan Maddamsetti},
url = {https://academic.oup.com/gbe/article/13/6/evab074/6240992},
doi = {https://doi.org/10.1093/gbe/evab074},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Genome Biology and Evolution},
volume = {13},
number = {6},
abstract = {Most cellular functions are carried out by a dynamic network of interacting proteins. An open question is whether the network properties of protein interactomes represent phenotypes under natural selection. One proposal is that protein interactomes have evolved to be resilient, such that they tend to maintain connectivity when proteins are removed from the network. This hypothesis predicts that interactome resilience should be maintained by natural selection during long-term experimental evolution. I tested this prediction by modeling the evolution of protein–protein interaction (PPI) networks in Lenski’s long-term evolution experiment with \textit{Escherichia coli} (LTEE). In this test, I removed proteins affected by nonsense, insertion, deletion, and transposon mutations in evolved LTEE strains, and measured the resilience of the resulting networks. I compared the rate of change of network resilience in each LTEE population to the rate of change of network resilience for corresponding randomized networks. The evolved PPI networks are significantly more resilient than networks in which random proteins have been deleted. Moreover, the evolved networks are generally more resilient than networks in which the random deletion of proteins was restricted to those disrupted in LTEE. These results suggest that evolution in the LTEE has favored PPI networks that are, on average, more resilient than expected from the genetic variation across the evolved strains. My findings therefore support the hypothesis that selection maintains protein interactome resilience over evolutionary time.},
keywords = {Genome Evolution, Genotypes and Phenotypes},
pubstate = {published},
tppubtype = {article}
}
Most cellular functions are carried out by a dynamic network of interacting proteins. An open question is whether the network properties of protein interactomes represent phenotypes under natural selection. One proposal is that protein interactomes have evolved to be resilient, such that they tend to maintain connectivity when proteins are removed from the network. This hypothesis predicts that interactome resilience should be maintained by natural selection during long-term experimental evolution. I tested this prediction by modeling the evolution of protein–protein interaction (PPI) networks in Lenski’s long-term evolution experiment with Escherichia coli (LTEE). In this test, I removed proteins affected by nonsense, insertion, deletion, and transposon mutations in evolved LTEE strains, and measured the resilience of the resulting networks. I compared the rate of change of network resilience in each LTEE population to the rate of change of network resilience for corresponding randomized networks. The evolved PPI networks are significantly more resilient than networks in which random proteins have been deleted. Moreover, the evolved networks are generally more resilient than networks in which the random deletion of proteins was restricted to those disrupted in LTEE. These results suggest that evolution in the LTEE has favored PPI networks that are, on average, more resilient than expected from the genetic variation across the evolved strains. My findings therefore support the hypothesis that selection maintains protein interactome resilience over evolutionary time.
Maddamsetti R
Universal Constraints on Protein Evolution in the Long-Term Evolution Experiment with Escherichia coli Journal Article
Genome Biology and Evolution, 13 (6), 2021.
Abstract | Links | BibTeX | Altmetric | Tags: Genome Evolution, Genotypes and Phenotypes
@article{Maddamsetti2021b,
title = {Universal Constraints on Protein Evolution in the Long-Term Evolution Experiment with \textit{Escherichia coli}},
author = {Rohan Maddamsetti},
url = {https://academic.oup.com/gbe/article/13/6/evab070/6226398},
doi = {https://doi.org/10.1093/gbe/evab070},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Genome Biology and Evolution},
volume = {13},
number = {6},
abstract = {Although it is well known that abundant proteins evolve slowly across the tree of life, there is little consensus for why this is true. Here, I report that abundant proteins evolve slowly in the hypermutator populations of Lenski’s long-term evolution experiment with \textit{Escherichia coli} (LTEE). Specifically, the density of all observed mutations per gene, as measured in metagenomic time series covering 60,000 generations of the LTEE, significantly anticorrelates with mRNA abundance, protein abundance, and degree of protein–protein interaction. The same pattern holds for nonsynonymous mutation density. However, synonymous mutation density, measured across the LTEE hypermutator populations, positively correlates with protein abundance. These results show that universal constraints on protein evolution are visible in data spanning three decades of experimental evolution. Therefore, it should be possible to design experiments to answer why abundant proteins evolve slowly.},
keywords = {Genome Evolution, Genotypes and Phenotypes},
pubstate = {published},
tppubtype = {article}
}
Although it is well known that abundant proteins evolve slowly across the tree of life, there is little consensus for why this is true. Here, I report that abundant proteins evolve slowly in the hypermutator populations of Lenski’s long-term evolution experiment with Escherichia coli (LTEE). Specifically, the density of all observed mutations per gene, as measured in metagenomic time series covering 60,000 generations of the LTEE, significantly anticorrelates with mRNA abundance, protein abundance, and degree of protein–protein interaction. The same pattern holds for nonsynonymous mutation density. However, synonymous mutation density, measured across the LTEE hypermutator populations, positively correlates with protein abundance. These results show that universal constraints on protein evolution are visible in data spanning three decades of experimental evolution. Therefore, it should be possible to design experiments to answer why abundant proteins evolve slowly.
Grant N A; abdel Magid A; Franklin J; Dufour Y; Lenski R E
Changes in cell size and shape during 50,000 generations of experimental evolution with Escherichia coli Journal Article
Journal of Bacteriology, 203 (10), pp. e00469-20, 2021.
Abstract | Links | BibTeX | Altmetric | Tags: Cell Morphology, Genotypes and Phenotypes
@article{Grant2021,
title = {Changes in cell size and shape during 50,000 generations of experimental evolution with \textit{Escherichia coli}},
author = {Nkrumah A. Grant and Ali {abdel Magid} and Joshua Franklin and Yann Dufour and Richard E. Lenski},
url = {https://journals.asm.org/doi/10.1128/JB.00469-20},
doi = {10.1128/JB.00469-20},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Journal of Bacteriology},
volume = {203},
number = {10},
pages = {e00469-20},
abstract = {Bacteria adopt a wide variety of sizes and shapes, with many species exhibiting stereotypical morphologies. How morphology changes, and over what timescales, is less clear. Previous work examining cell morphology in an experiment with \textit{Escherichia coli} showed that populations evolved larger cells and, in some cases, cells that were less rod-like. That experiment has now run for over two more decades. Meanwhile, genome sequence data are available for these populations, and new computational methods enable high-throughput microscopic analyses. In this study, we measured stationary-phase cell volumes for the ancestor and 12 populations at 2,000, 10,000, and 50,000 generations, including measurements during exponential growth at the last time point. We measured the distribution of cell volumes for each sample using a Coulter counter and microscopy, the latter of which also provided data on cell shape. Our data confirm the trend toward larger cells while also revealing substantial variation in size and shape across replicate populations. Most populations first evolved wider cells but later reverted to the ancestral length-to-width ratio. All but one population evolved mutations in rod shape maintenance genes. We also observed many ghost-like cells in the only population that evolved the novel ability to grow on citrate, supporting the hypothesis that this lineage struggles with maintaining balanced growth. Lastly, we show that cell size and fitness remain correlated across 50,000 generations. Our results suggest that larger cells are beneficial in the experimental environment, while the reversion toward ancestral length-to-width ratios suggests partial compensation for the less favorable surface area-to-volume ratios of the evolved cells.},
keywords = {Cell Morphology, Genotypes and Phenotypes},
pubstate = {published},
tppubtype = {article}
}
Bacteria adopt a wide variety of sizes and shapes, with many species exhibiting stereotypical morphologies. How morphology changes, and over what timescales, is less clear. Previous work examining cell morphology in an experiment with Escherichia coli showed that populations evolved larger cells and, in some cases, cells that were less rod-like. That experiment has now run for over two more decades. Meanwhile, genome sequence data are available for these populations, and new computational methods enable high-throughput microscopic analyses. In this study, we measured stationary-phase cell volumes for the ancestor and 12 populations at 2,000, 10,000, and 50,000 generations, including measurements during exponential growth at the last time point. We measured the distribution of cell volumes for each sample using a Coulter counter and microscopy, the latter of which also provided data on cell shape. Our data confirm the trend toward larger cells while also revealing substantial variation in size and shape across replicate populations. Most populations first evolved wider cells but later reverted to the ancestral length-to-width ratio. All but one population evolved mutations in rod shape maintenance genes. We also observed many ghost-like cells in the only population that evolved the novel ability to grow on citrate, supporting the hypothesis that this lineage struggles with maintaining balanced growth. Lastly, we show that cell size and fitness remain correlated across 50,000 generations. Our results suggest that larger cells are beneficial in the experimental environment, while the reversion toward ancestral length-to-width ratios suggests partial compensation for the less favorable surface area-to-volume ratios of the evolved cells.
Gifford I; Dasgupta A; Barrick J E
Rates of gene conversions between Escherichia coli ribosomal operons Journal Article
G3: Genes, Genomes, Genetics, 11 (2), 2021, ISSN: 21601836.
Abstract | Links | BibTeX | Altmetric | Tags: Descendant Experiments, Mutation Rates
@article{Gifford2021,
title = {Rates of gene conversions between \emph{Escherichia coli} ribosomal operons},
author = {Isaac Gifford and Aurko Dasgupta and Jeffrey E. Barrick},
url = {https://academic.oup.com/g3journal/article/11/2/jkaa002/5974039},
doi = {10.1093/g3journal/jkaa002},
issn = {21601836},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {G3: Genes, Genomes, Genetics},
volume = {11},
number = {2},
abstract = {Due to their universal presence and high sequence conservation, ribosomal RNA (rRNA) sequences are used widely in phylogenetics for inferring evolutionary relationships between microbes and in metagenomics for analyzing the composition of microbial communities. Most microbial genomes encode multiple copies of rRNA genes to supply cells with sufficient capacity for protein synthesis. These copies typically undergo concerted evolution that keeps their sequences identical, or nearly so, due to gene conversion, a type of intragenomic recombination that changes one copy of a homologous sequence to exactly match another. Widely varying rates of rRNA gene conversion have previously been estimated by comparative genomics methods and using genetic reporter assays. To more directly measure rates of rRNA intragenomic recombination, we sequenced the seven \textit{Escherichia coli} rRNA operons in 15 lineages that were evolved for ~13,750 generations with frequent single-cell bottlenecks that reduce the effects of selection. We identified 38 gene conversion events and estimated an overall rate of intragenomic recombination within the 16S and 23S genes between rRNA copies of 3.6 × 10^{−4} per genome per generation or 8.6 × 10^{6} per rRNA operon per homologous donor operon per generation. This rate varied only slightly from random expectations at different sites within the rRNA genes and between rRNA operons located at different positions in the genome. Our accurate estimate of the rate of rRNA gene conversions fills a gap in our quantitative understanding of how ribosomal sequences and other multicopy elements diversify and homogenize during microbial genome evolution.},
keywords = {Descendant Experiments, Mutation Rates},
pubstate = {published},
tppubtype = {article}
}
Due to their universal presence and high sequence conservation, ribosomal RNA (rRNA) sequences are used widely in phylogenetics for inferring evolutionary relationships between microbes and in metagenomics for analyzing the composition of microbial communities. Most microbial genomes encode multiple copies of rRNA genes to supply cells with sufficient capacity for protein synthesis. These copies typically undergo concerted evolution that keeps their sequences identical, or nearly so, due to gene conversion, a type of intragenomic recombination that changes one copy of a homologous sequence to exactly match another. Widely varying rates of rRNA gene conversion have previously been estimated by comparative genomics methods and using genetic reporter assays. To more directly measure rates of rRNA intragenomic recombination, we sequenced the seven Escherichia coli rRNA operons in 15 lineages that were evolved for ~13,750 generations with frequent single-cell bottlenecks that reduce the effects of selection. We identified 38 gene conversion events and estimated an overall rate of intragenomic recombination within the 16S and 23S genes between rRNA copies of 3.6 × 10−4 per genome per generation or 8.6 × 106 per rRNA operon per homologous donor operon per generation. This rate varied only slightly from random expectations at different sites within the rRNA genes and between rRNA operons located at different positions in the genome. Our accurate estimate of the rate of rRNA gene conversions fills a gap in our quantitative understanding of how ribosomal sequences and other multicopy elements diversify and homogenize during microbial genome evolution.
2020
Atolia E; Cesar S; Arjes H A; Rajendram M; Shi H; Knapp B D; Khare S; Aranda-Díaz A; Lenski R E; Huang K C
Environmental and Physiological Factors Affecting High-Throughput Measurements of Bacterial Growth Journal Article
mBio, 11 (5), pp. 1–19, 2020, ISSN: 2161-2129.
Abstract | Links | BibTeX | Altmetric | Tags: Demography and Ecology
@article{Atolia2020,
title = {Environmental and Physiological Factors Affecting High-Throughput Measurements of Bacterial Growth},
author = {Esha Atolia and Spencer Cesar and Heidi A Arjes and Manohary Rajendram and Handuo Shi and Benjamin D Knapp and Somya Khare and Andrés Aranda-Díaz and Richard E. Lenski and Kerwyn Casey Huang},
editor = {Kelly T. Hughes},
url = {https://journals.asm.org/doi/10.1128/mBio.01378-20},
doi = {10.1128/mBio.01378-20},
issn = {2161-2129},
year = {2020},
date = {2020-10-01},
urldate = {2020-10-01},
journal = {mBio},
volume = {11},
number = {5},
pages = {1--19},
abstract = {How starved bacteria adapt and multiply under replete nutrient conditions is intimately linked to their history of previous growth, their physiological state, and the surrounding environment. While automated equipment has enabled high-throughput growth measurements, data interpretation and knowledge gaps regarding the determinants of growth kinetics complicate comparisons between strains. Here, we present a framework for growth measurements that improves accuracy and attenuates the effects of growth history. We determined that background absorbance quantification and multiple passaging cycles allow for accurate growth rate measurements even in carbon-poor media, which we used to reveal growth-rate increases during long-term laboratory evolution of \textit{Escherichia coli}. Using mathematical modeling, we showed that maximum growth rate depends on initial cell density. Finally, we demonstrated that growth of Bacillus subtilis with glycerol inhibits the future growth of most of the population, due to lipoteichoic acid synthesis. These studies highlight the challenges of accurate quantification of bacterial growth behaviors.},
keywords = {Demography and Ecology},
pubstate = {published},
tppubtype = {article}
}
How starved bacteria adapt and multiply under replete nutrient conditions is intimately linked to their history of previous growth, their physiological state, and the surrounding environment. While automated equipment has enabled high-throughput growth measurements, data interpretation and knowledge gaps regarding the determinants of growth kinetics complicate comparisons between strains. Here, we present a framework for growth measurements that improves accuracy and attenuates the effects of growth history. We determined that background absorbance quantification and multiple passaging cycles allow for accurate growth rate measurements even in carbon-poor media, which we used to reveal growth-rate increases during long-term laboratory evolution of Escherichia coli. Using mathematical modeling, we showed that maximum growth rate depends on initial cell density. Finally, we demonstrated that growth of Bacillus subtilis with glycerol inhibits the future growth of most of the population, due to lipoteichoic acid synthesis. These studies highlight the challenges of accurate quantification of bacterial growth behaviors.
Maddamsetti R; Grant N A
Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli Journal Article
Genome Biology and Evolution, 12 (9), pp. 1591-1603, 2020, ISSN: 1759-6653.
Abstract | Links | BibTeX | Altmetric | Tags: Genome Evolution, Mutation Rates
@article{nokey,
title = {Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with \textit{Escherichia coli}},
author = {Rohan Maddamsetti and Nkrumah A. Grant},
editor = {George Zhang},
url = {https://academic.oup.com/gbe/article/12/9/1591/5898197},
doi = {10.1093/gbe/evaa178},
issn = {1759-6653},
year = {2020},
date = {2020-08-21},
urldate = {2020-08-21},
journal = {Genome Biology and Evolution},
volume = {12},
number = {9},
pages = {1591-1603},
abstract = {All organisms encode enzymes that replicate, maintain, pack, recombine, and repair their genetic material. For this reason, mutation rates and biases also evolve by mutation, variation, and natural selection. By examining metagenomic time series of the Lenski long-term evolution experiment (LTEE) with \textit{Escherichia coli} (Good BH, McDonald MJ, Barrick JE, Lenski RE, Desai MM. 2017. The dynamics of molecular evolution over 60,000 generations. Nature 551(7678):45–50.), we find that local mutation rate variation has evolved during the LTEE. Each LTEE population has evolved idiosyncratic differences in their rates of point mutations, indels, and mobile element insertions, due to the fixation of various hypermutator and antimutator alleles. One LTEE population, called Ara+3, shows a strong, symmetric wave pattern in its density of point mutations, radiating from the origin of replication. This pattern is largely missing from the other LTEE populations, most of which evolved missense, indel, or structural mutations in \textit{topA}, \textit{fis}, and \textit{dusB}—loci that all affect DNA topology. The distribution of mutations in those genes over time suggests epistasis and historical contingency in the evolution of DNA topology, which may have in turn affected local mutation rates. Overall, the replicate populations of the LTEE have largely diverged in their mutation rates and biases, even though they have adapted to identical abiotic conditions.},
keywords = {Genome Evolution, Mutation Rates},
pubstate = {published},
tppubtype = {article}
}
All organisms encode enzymes that replicate, maintain, pack, recombine, and repair their genetic material. For this reason, mutation rates and biases also evolve by mutation, variation, and natural selection. By examining metagenomic time series of the Lenski long-term evolution experiment (LTEE) with Escherichia coli (Good BH, McDonald MJ, Barrick JE, Lenski RE, Desai MM. 2017. The dynamics of molecular evolution over 60,000 generations. Nature 551(7678):45–50.), we find that local mutation rate variation has evolved during the LTEE. Each LTEE population has evolved idiosyncratic differences in their rates of point mutations, indels, and mobile element insertions, due to the fixation of various hypermutator and antimutator alleles. One LTEE population, called Ara+3, shows a strong, symmetric wave pattern in its density of point mutations, radiating from the origin of replication. This pattern is largely missing from the other LTEE populations, most of which evolved missense, indel, or structural mutations in topA, fis, and dusB—loci that all affect DNA topology. The distribution of mutations in those genes over time suggests epistasis and historical contingency in the evolution of DNA topology, which may have in turn affected local mutation rates. Overall, the replicate populations of the LTEE have largely diverged in their mutation rates and biases, even though they have adapted to identical abiotic conditions.
Blount Z D; Maddamsetti R; Grant N A; Ahmed S T; Jagdish T; Baxter J A; Sommerfeld B A; Tillman A; Moore J; Slonczewski J L; Barrick J E; Lenski R E
Genomic and phenotypic evolution of Escherichia coli in a novel citrate-only resource environment Journal Article
eLife, 9 , pp. 1–64, 2020, ISSN: 2050-084X.
Abstract | Links | BibTeX | Altmetric | Tags: Citrate Evolution, Demography and Ecology, Descendant Experiments, Genotypes and Phenotypes
@article{Blount2020,
title = {Genomic and phenotypic evolution of \textit{Escherichia coli} in a novel citrate-only resource environment},
author = {Zachary D. Blount and Rohan Maddamsetti and Nkrumah A. Grant and Sumaya T. Ahmed and Tanush Jagdish and Jessica A. Baxter and Brooke A. Sommerfeld and Alice Tillman and Jeremy Moore and Joan L. Slonczewski and Jeffrey E. Barrick and Richard E. Lenski},
url = {https://elifesciences.org/articles/55414},
doi = {10.7554/eLife.55414},
issn = {2050-084X},
year = {2020},
date = {2020-05-01},
urldate = {2020-05-01},
journal = {eLife},
volume = {9},
pages = {1--64},
abstract = {Evolutionary innovations allow populations to colonize new ecological niches. We previously reported that aerobic growth on citrate (Cit^{+}) evolved in an \textit{Escherichia coli} population during adaptation to a minimal glucose medium containing citrate (DM25). Cit^{+} variants can also grow in citrate-only medium (DM0), a novel environment for \textit{E. coli}. To study adaptation to this niche, we founded two sets of Cit^{+} populations and evolved them for 2500 generations in DM0 or DM25. The evolved lineages acquired numerous parallel mutations, many mediated by transposable elements. Several also evolved amplifications of regions containing the \textit{maeA} gene. Unexpectedly, some evolved populations and clones show apparent declines in fitness. We also found evidence of substantial cell death in Cit^{+} clones. Our results thus demonstrate rapid trait refinement and adaptation to the new citrate niche, while also suggesting a recalcitrant mismatch between \textit{E. coli} physiology and growth on citrate.},
keywords = {Citrate Evolution, Demography and Ecology, Descendant Experiments, Genotypes and Phenotypes},
pubstate = {published},
tppubtype = {article}
}
Evolutionary innovations allow populations to colonize new ecological niches. We previously reported that aerobic growth on citrate (Cit+) evolved in an Escherichia coli population during adaptation to a minimal glucose medium containing citrate (DM25). Cit+ variants can also grow in citrate-only medium (DM0), a novel environment for E. coli. To study adaptation to this niche, we founded two sets of Cit+ populations and evolved them for 2500 generations in DM0 or DM25. The evolved lineages acquired numerous parallel mutations, many mediated by transposable elements. Several also evolved amplifications of regions containing the maeA gene. Unexpectedly, some evolved populations and clones show apparent declines in fitness. We also found evidence of substantial cell death in Cit+ clones. Our results thus demonstrate rapid trait refinement and adaptation to the new citrate niche, while also suggesting a recalcitrant mismatch between E. coli physiology and growth on citrate.
Barrick J E; Deatherage D E; Lenski R E
Banzhaf, Wolfgang; Cheng, Betty H C; Deb, Kalyanmoy; Holekamp, Kay E; Lenski, Richard E; Ofria, Charles; Pennock, Robert T; Punch, William F; Whittaker, Danielle J (Ed.): Evolution in Action: Past, Present and Future: A Festschrift in Honor of Erik D. Goodman, pp. 77–89, Springer International Publishing, Cham, 2020, ISBN: 978-3-030-39831-6.
Abstract | Links | BibTeX | Altmetric | Tags: Fitness Trajectories
@inbook{Barrick2020,
title = {A Test of the Repeatability of Measurements of Relative Fitness in the Long-Term Evolution Experiment with \textit{Escherichia coli}},
author = {Jeffrey E. Barrick and Daniel E. Deatherage and Richard E. Lenski},
editor = {Wolfgang Banzhaf and Betty H C Cheng and Kalyanmoy Deb and Kay E Holekamp and Richard E Lenski and Charles Ofria and Robert T Pennock and William F Punch and Danielle J Whittaker},
url = {http://link.springer.com/10.1007/978-3-030-39831-6_8},
doi = {10.1007/978-3-030-39831-6_8},
isbn = {978-3-030-39831-6},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
booktitle = {Evolution in Action: Past, Present and Future: A Festschrift in Honor of Erik D. Goodman},
pages = {77--89},
publisher = {Springer International Publishing},
address = {Cham},
abstract = {Experimental studies of evolution using microbes have a long tradition, and these studies have increased greatly in number and scope in recent decades. Most such experiments have been short in duration, typically running for weeks or months. A venerable exception, the long-term evolution experiment (LTEE) with \textit{Escherichia coli} has continued for 30 years and 70,000 bacterial generations. The LTEE has become one of the cornerstones of the field of experimental evolution, in general, and the BEACON Center for the Study of Evolution in Action, in particular. Science laboratories and experiments usually have finite lifespans, but we hope that the LTEE can continue far into the future. There are practical issues associated with maintaining such a long-term experiment. One issue, which we address here, is whether key measurements made at one time and place are reproducible, within reasonable limits, at other times and places. This issue comes to the forefront when one considers moving an experiment like the LTEE from one lab to another. To that end, the Barrick lab at The University of Texas at Austin, measured the fitness values of samples from the 12 LTEE populations at 2,000, 10,000, and 50,000 generations and compared the new data to data previously obtained at Michigan State University. On balance, the datasets agree very well. More generally, this finding shows the value of simplicity in experimental design, such as using a chemically defined growth medium and appropriately storing samples from microbiological experiments. Even so, one must be vigilant in checking assumptions and procedures given the potential for uncontrolled factors (e.g., water quality) to affect outcomes. This vigilance is perhaps especially important for a trait like fitness, which integrates all aspects of organismal performance and may therefore be sensitive to any number of subtle environmental influences.},
keywords = {Fitness Trajectories},
pubstate = {published},
tppubtype = {inbook}
}
Experimental studies of evolution using microbes have a long tradition, and these studies have increased greatly in number and scope in recent decades. Most such experiments have been short in duration, typically running for weeks or months. A venerable exception, the long-term evolution experiment (LTEE) with Escherichia coli has continued for 30 years and 70,000 bacterial generations. The LTEE has become one of the cornerstones of the field of experimental evolution, in general, and the BEACON Center for the Study of Evolution in Action, in particular. Science laboratories and experiments usually have finite lifespans, but we hope that the LTEE can continue far into the future. There are practical issues associated with maintaining such a long-term experiment. One issue, which we address here, is whether key measurements made at one time and place are reproducible, within reasonable limits, at other times and places. This issue comes to the forefront when one considers moving an experiment like the LTEE from one lab to another. To that end, the Barrick lab at The University of Texas at Austin, measured the fitness values of samples from the 12 LTEE populations at 2,000, 10,000, and 50,000 generations and compared the new data to data previously obtained at Michigan State University. On balance, the datasets agree very well. More generally, this finding shows the value of simplicity in experimental design, such as using a chemically defined growth medium and appropriately storing samples from microbiological experiments. Even so, one must be vigilant in checking assumptions and procedures given the potential for uncontrolled factors (e.g., water quality) to affect outcomes. This vigilance is perhaps especially important for a trait like fitness, which integrates all aspects of organismal performance and may therefore be sensitive to any number of subtle environmental influences.
2019
Card K J; LaBar T; Gomez J B; Lenski R E
Historical contingency in the evolution of antibiotic resistance after decades of relaxed selection Journal Article
PLOS Biology, 17 (10), pp. e3000397, 2019, ISSN: 1545-7885.
Abstract | Links | BibTeX | Altmetric | Tags: Correlated Responses, Descendant Experiments, Historical Contingency
@article{nokey,
title = {Historical contingency in the evolution of antibiotic resistance after decades of relaxed selection},
author = {Kyle J. Card and Thomas LaBar and Jasper B. Gomez and Richard E. Lenski},
url = {https://dx.plos.org/10.1371/journal.pbio.3000397},
doi = {10.1371/journal.pbio.3000397},
issn = {1545-7885},
year = {2019},
date = {2019-10-23},
urldate = {2019-10-23},
journal = {PLOS Biology},
volume = {17},
number = {10},
pages = {e3000397},
abstract = {Populations often encounter changed environments that remove selection for the maintenance of particular phenotypic traits. The resulting genetic decay of those traits under relaxed selection reduces an organism’s fitness in its prior environment. However, whether and how such decay alters the subsequent evolvability of a population upon restoration of selection for a previously diminished trait is not well understood. We addressed this question using \textit{Escherichia coli} strains from the long-term evolution experiment (LTEE) that independently evolved for multiple decades in the absence of antibiotics. We first confirmed that these derived strains are typically more sensitive to various antibiotics than their common ancestor. We then subjected the ancestral and derived strains to various concentrations of these drugs to examine their potential to evolve increased resistance. We found that evolvability was idiosyncratic with respect to initial genotype; that is, the derived strains did not generally compensate for their greater susceptibility by “catching up” to the resistance level of the ancestor. Instead, the capacity to evolve increased resistance was constrained in some backgrounds, implying that evolvability depended upon prior mutations in a historically contingent fashion. We further subjected a time series of clones from one LTEE population to tetracycline and determined that an evolutionary constraint arose early in that population, corroborating the role of contingency. In summary, relaxed selection not only can drive populations to increased antibiotic susceptibility, but it can also affect the subsequent evolvability of antibiotic resistance in an unpredictable manner. This conclusion has potential implications for public health, and it underscores the need to consider the genetic context of pathogens when designing drug-treatment strategies.},
keywords = {Correlated Responses, Descendant Experiments, Historical Contingency},
pubstate = {published},
tppubtype = {article}
}
Populations often encounter changed environments that remove selection for the maintenance of particular phenotypic traits. The resulting genetic decay of those traits under relaxed selection reduces an organism’s fitness in its prior environment. However, whether and how such decay alters the subsequent evolvability of a population upon restoration of selection for a previously diminished trait is not well understood. We addressed this question using Escherichia coli strains from the long-term evolution experiment (LTEE) that independently evolved for multiple decades in the absence of antibiotics. We first confirmed that these derived strains are typically more sensitive to various antibiotics than their common ancestor. We then subjected the ancestral and derived strains to various concentrations of these drugs to examine their potential to evolve increased resistance. We found that evolvability was idiosyncratic with respect to initial genotype; that is, the derived strains did not generally compensate for their greater susceptibility by “catching up” to the resistance level of the ancestor. Instead, the capacity to evolve increased resistance was constrained in some backgrounds, implying that evolvability depended upon prior mutations in a historically contingent fashion. We further subjected a time series of clones from one LTEE population to tetracycline and determined that an evolutionary constraint arose early in that population, corroborating the role of contingency. In summary, relaxed selection not only can drive populations to increased antibiotic susceptibility, but it can also affect the subsequent evolvability of antibiotic resistance in an unpredictable manner. This conclusion has potential implications for public health, and it underscores the need to consider the genetic context of pathogens when designing drug-treatment strategies.
Lamrabet O; Plumbridge J; Martin M; Lenski R E; Schneider D; Hindré T
Plasticity of Promoter-Core Sequences Allows Bacteria to Compensate for the Loss of a Key Global Regulatory Gene Journal Article
Molecular Biology and Evolution, 36 (6), pp. 1121–1133, 2019, ISSN: 0737-4038.
Abstract | Links | BibTeX | Altmetric | Tags: Descendant Experiments
@article{Lamrabet2019b,
title = {Plasticity of Promoter-Core Sequences Allows Bacteria to Compensate for the Loss of a Key Global Regulatory Gene},
author = {Otmane Lamrabet and Jacqueline Plumbridge and Mikaël Martin and Richard E. Lenski and Dominique Schneider and Thomas Hindré},
editor = {Csaba Pal},
url = {https://academic.oup.com/mbe/article/36/6/1121/5368491},
doi = {10.1093/molbev/msz042},
issn = {0737-4038},
year = {2019},
date = {2019-06-01},
urldate = {2019-06-01},
journal = {Molecular Biology and Evolution},
volume = {36},
number = {6},
pages = {1121--1133},
abstract = {Transcription regulatory networks (TRNs) are of central importance for both short-term phenotypic adaptation in response to environmental fluctuations and long-term evolutionary adaptation, with global regulatory genes often being targets of natural selection in laboratory experiments. Here, we combined evolution experiments, whole-genome resequencing, and molecular genetics to investigate the driving forces, genetic constraints, and molecular mechanisms that dictate how bacteria can cope with a drastic perturbation of their TRNs. The \textit{crp} gene, encoding a major global regulator in \textit{Escherichia coli}, was deleted in four different genetic backgrounds, all derived from the Long-Term Evolution Experiment (LTEE) but with different TRN architectures. We confirmed that \textit{crp} deletion had a more deleterious effect on growth rate in the LTEE-adapted genotypes; and we showed that the \textit{ptsG} gene, which encodes the major glucose-PTS transporter, gained CRP (cyclic AMP receptor protein) dependence over time in the LTEE. We then further evolved the four \textit{crp}-deleted genotypes in glucose minimal medium, and we found that they all quickly recovered from their growth defects by increasing glucose uptake. We showed that this recovery was specific to the selective environment and consistently relied on mutations in the cis-regulatory region of \textit{ptsG}, regardless of the initial genotype. These mutations affected the interplay of transcription factors acting at the promoters, changed the intrinsic properties of the existing promoters, or produced new transcription initiation sites. Therefore, the plasticity of even a single promoter region can compensate by three different mechanisms for the loss of a key regulatory hub in the \textit{E. coli} TRN.},
keywords = {Descendant Experiments},
pubstate = {published},
tppubtype = {article}
}
Transcription regulatory networks (TRNs) are of central importance for both short-term phenotypic adaptation in response to environmental fluctuations and long-term evolutionary adaptation, with global regulatory genes often being targets of natural selection in laboratory experiments. Here, we combined evolution experiments, whole-genome resequencing, and molecular genetics to investigate the driving forces, genetic constraints, and molecular mechanisms that dictate how bacteria can cope with a drastic perturbation of their TRNs. The crp gene, encoding a major global regulator in Escherichia coli, was deleted in four different genetic backgrounds, all derived from the Long-Term Evolution Experiment (LTEE) but with different TRN architectures. We confirmed that crp deletion had a more deleterious effect on growth rate in the LTEE-adapted genotypes; and we showed that the ptsG gene, which encodes the major glucose-PTS transporter, gained CRP (cyclic AMP receptor protein) dependence over time in the LTEE. We then further evolved the four crp-deleted genotypes in glucose minimal medium, and we found that they all quickly recovered from their growth defects by increasing glucose uptake. We showed that this recovery was specific to the selective environment and consistently relied on mutations in the cis-regulatory region of ptsG, regardless of the initial genotype. These mutations affected the interplay of transcription factors acting at the promoters, changed the intrinsic properties of the existing promoters, or produced new transcription initiation sites. Therefore, the plasticity of even a single promoter region can compensate by three different mechanisms for the loss of a key regulatory hub in the E. coli TRN.
Lamrabet O; Martin M; Lenski R E; Schneider D
Changes in Intrinsic Antibiotic Susceptibility during a Long-Term Evolution Experiment with Escherichia coli Journal Article
mBio, 10 (2), pp. 1–12, 2019, ISSN: 2161-2129.
Abstract | Links | BibTeX | Altmetric | Tags: Correlated Responses
@article{Lamrabet2019,
title = {Changes in Intrinsic Antibiotic Susceptibility during a Long-Term Evolution Experiment with \textit{Escherichia coli}},
author = {Otmane Lamrabet and Mikaël Martin and Richard E. Lenski and Dominique Schneider},
editor = {Julian E. Davies},
url = {https://journals.asm.org/doi/10.1128/mBio.00189-19},
doi = {10.1128/mBio.00189-19},
issn = {2161-2129},
year = {2019},
date = {2019-04-01},
urldate = {2019-04-01},
journal = {mBio},
volume = {10},
number = {2},
pages = {1--12},
abstract = {Resistance to antibiotics often evolves when bacteria encounter antibiotics. However, bacterial strains and species without any known exposure to these drugs also vary in their intrinsic susceptibility. In many cases, evolved resistance has been shown to be costly to the bacteria, such that resistant types have reduced competitiveness relative to their sensitive progenitors in the absence of antibiotics. In this study, we examined changes in the susceptibilities of 12 populations of \textit{Escherichia coli} to 15 antibiotics after 2,000 and 50,000 generations without exposure to any drug. The evolved bacteria tended to become more susceptible to most antibiotics, with most of the change occurring during the first 2,000 generations, when the bacteria were undergoing rapid adaptation to their experimental conditions. On balance, our findings indicate that bacteria with low levels of intrinsic resistance can, in the absence of relevant selection, become even more susceptible to antibiotics.},
keywords = {Correlated Responses},
pubstate = {published},
tppubtype = {article}
}
Resistance to antibiotics often evolves when bacteria encounter antibiotics. However, bacterial strains and species without any known exposure to these drugs also vary in their intrinsic susceptibility. In many cases, evolved resistance has been shown to be costly to the bacteria, such that resistant types have reduced competitiveness relative to their sensitive progenitors in the absence of antibiotics. In this study, we examined changes in the susceptibilities of 12 populations of Escherichia coli to 15 antibiotics after 2,000 and 50,000 generations without exposure to any drug. The evolved bacteria tended to become more susceptible to most antibiotics, with most of the change occurring during the first 2,000 generations, when the bacteria were undergoing rapid adaptation to their experimental conditions. On balance, our findings indicate that bacteria with low levels of intrinsic resistance can, in the absence of relevant selection, become even more susceptible to antibiotics.
2018
Blount Z D; Lenski R E; Losos J B
Contingency and determinism in evolution: Replaying life's tape Journal Article
Science, 362 (6415), pp. eaam5979, 2018, ISSN: 0036-8075.
Abstract | Links | BibTeX | Altmetric | Tags: Historical Contingency, Parallelism and Divergence, Review Articles
@article{Blount2018,
title = {Contingency and determinism in evolution: Replaying life's tape},
author = {Zachary D. Blount and Richard E. Lenski and Jonathan B. Losos},
url = {https://www.sciencemag.org/lookup/doi/10.1126/science.aam5979},
doi = {10.1126/science.aam5979},
issn = {0036-8075},
year = {2018},
date = {2018-11-01},
urldate = {2018-11-01},
journal = {Science},
volume = {362},
number = {6415},
pages = {eaam5979},
abstract = {Historical processes display some degree of "contingency," meaning their outcomes are sensitive to seemingly inconsequential events that can fundamentally change the future. Contingency is what makes historical outcomes unpredictable. Unlike many other natural phenomena, evolution is a historical process. Evolutionary change is often driven by the deterministic force of natural selection, but natural selection works upon variation that arises unpredictably through time by random mutation, and even beneficial mutations can be lost by chance through genetic drift. Moreover, evolution has taken place within a planetary environment with a particular history of its own. This tension between determinism and contingency makes evolutionary biology a kind of hybrid between science and history. While philosophers of science examine the nuances of contingency, biologists have performed many empirical studies of evolutionary repeatability and contingency. Here, we review the experimental and comparative evidence from these studies. Replicate populations in evolutionary "replay" experiments often show parallel changes, especially in overall performance, although idiosyncratic outcomes show that the particulars of a lineage's history can affect which of several evolutionary paths is taken. Comparative biologists have found many notable examples of convergent adaptation to similar conditions, but quantification of how frequently such convergence occurs is difficult. On balance, the evidence indicates that evolution tends to be surprisingly repeatable among closely related lineages, but disparate outcomes become more likely as the footprint of history grows deeper. Ongoing research on the structure of adaptive landscapes is providing additional insight into the interplay of fate and chance in the evolutionary process.},
keywords = {Historical Contingency, Parallelism and Divergence, Review Articles},
pubstate = {published},
tppubtype = {article}
}
Historical processes display some degree of "contingency," meaning their outcomes are sensitive to seemingly inconsequential events that can fundamentally change the future. Contingency is what makes historical outcomes unpredictable. Unlike many other natural phenomena, evolution is a historical process. Evolutionary change is often driven by the deterministic force of natural selection, but natural selection works upon variation that arises unpredictably through time by random mutation, and even beneficial mutations can be lost by chance through genetic drift. Moreover, evolution has taken place within a planetary environment with a particular history of its own. This tension between determinism and contingency makes evolutionary biology a kind of hybrid between science and history. While philosophers of science examine the nuances of contingency, biologists have performed many empirical studies of evolutionary repeatability and contingency. Here, we review the experimental and comparative evidence from these studies. Replicate populations in evolutionary "replay" experiments often show parallel changes, especially in overall performance, although idiosyncratic outcomes show that the particulars of a lineage's history can affect which of several evolutionary paths is taken. Comparative biologists have found many notable examples of convergent adaptation to similar conditions, but quantification of how frequently such convergence occurs is difficult. On balance, the evidence indicates that evolution tends to be surprisingly repeatable among closely related lineages, but disparate outcomes become more likely as the footprint of history grows deeper. Ongoing research on the structure of adaptive landscapes is providing additional insight into the interplay of fate and chance in the evolutionary process.
Bajić D; Vila J C C; Blount Z D; Sánchez A
On the deformability of an empirical fitness landscape by microbial evolution Journal Article
Proceedings of the National Academy of Sciences, 115 (44), pp. 11286-11291, 2018, ISSN: 0027-8424.
Abstract | Links | BibTeX | Altmetric | Tags: Citrate Evolution, Demography and Ecology, Theory and Simulations
@article{nokey,
title = {On the deformability of an empirical fitness landscape by microbial evolution},
author = {Djordje Bajić and Jean C. C. Vila and Zachary D. Blount and Alvaro Sánchez},
url = {http://www.pnas.org/lookup/doi/10.1073/pnas.1808485115},
doi = {10.1073/pnas.1808485115},
issn = {0027-8424},
year = {2018},
date = {2018-10-30},
urldate = {2018-10-30},
journal = {Proceedings of the National Academy of Sciences},
volume = {115},
number = {44},
pages = {11286-11291},
abstract = {A fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Theory suggests that this topography can be deformed by mutations that produce substantial changes to the environment. Despite its importance, the deformability of fitness landscapes has not been systematically studied beyond abstract models, and little is known about its reach and consequences in empirical systems. Here we have systematically characterized the deformability of the genome-wide metabolic fitness landscape of the bacterium \textit{Escherichia coli}. Deformability is quantified by the noncommutativity of epistatic interactions, which we experimentally demonstrate in mutant strains on the path to an evolutionary innovation. Our analysis shows that the deformation of fitness landscapes by metabolic mutations rarely affects evolutionary trajectories in the short range. However, mutations with large environmental effects produce long-range landscape deformations in distant regions of the genotype space that affect the fitness of later descendants. Our results therefore suggest that, even in situations in which mutations have strong environmental effects, fitness landscapes may retain their power to forecast evolution over small mutational distances despite the potential attenuation of that power over longer evolutionary trajectories. Our methods and results provide an avenue for integrating adaptive and eco-evolutionary dynamics with complex genetics and genomics. },
keywords = {Citrate Evolution, Demography and Ecology, Theory and Simulations},
pubstate = {published},
tppubtype = {article}
}
A fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Theory suggests that this topography can be deformed by mutations that produce substantial changes to the environment. Despite its importance, the deformability of fitness landscapes has not been systematically studied beyond abstract models, and little is known about its reach and consequences in empirical systems. Here we have systematically characterized the deformability of the genome-wide metabolic fitness landscape of the bacterium Escherichia coli. Deformability is quantified by the noncommutativity of epistatic interactions, which we experimentally demonstrate in mutant strains on the path to an evolutionary innovation. Our analysis shows that the deformation of fitness landscapes by metabolic mutations rarely affects evolutionary trajectories in the short range. However, mutations with large environmental effects produce long-range landscape deformations in distant regions of the genotype space that affect the fitness of later descendants. Our results therefore suggest that, even in situations in which mutations have strong environmental effects, fitness landscapes may retain their power to forecast evolution over small mutational distances despite the potential attenuation of that power over longer evolutionary trajectories. Our methods and results provide an avenue for integrating adaptive and eco-evolutionary dynamics with complex genetics and genomics.
Leon D; D'Alton S; Quandt E M; Barrick J E
Innovation in an E. coli evolution experiment is contingent on maintaining adaptive potential until competition subsides Journal Article
PLOS Genetics, 14 (4), pp. e1007348, 2018, ISSN: 1553-7404.
Abstract | Links | BibTeX | Altmetric | Tags: Citrate Evolution, Demography and Ecology, Historical Contingency
@article{nokey,
title = {Innovation in an \textit{E. coli} evolution experiment is contingent on maintaining adaptive potential until competition subsides},
author = {Dacia Leon and Simon D'Alton and Erik M. Quandt and Jeffrey E. Barrick},
url = {https://dx.plos.org/10.1371/journal.pgen.1007348},
doi = {10.1371/journal.pgen.1007348},
issn = {1553-7404},
year = {2018},
date = {2018-04-12},
urldate = {2018-04-12},
journal = {PLOS Genetics},
volume = {14},
number = {4},
pages = {e1007348},
abstract = {Key innovations are disruptive evolutionary events that enable a species to escape constraints and rapidly diversify. After 15 years of the Lenski long-term evolution experiment with \textit{Escherichia coli}, cells in one of the twelve populations evolved the ability to utilize citrate, an abundant but previously untapped carbon source in the environment. Descendants of these cells became dominant in the population and subsequently diversified as a consequence of invading this vacant niche. Mutations responsible for the appearance of rudimentary citrate utilization and for refining this ability have been characterized. However, the complete nature of the genetic and/or ecological events that set the stage for this key innovation is unknown. In particular, it is unclear why it took so long for citrate utilization to evolve and why it still has evolved in only one of the twelve \textit{E. coli} populations after 30 years of the Lenski experiment. In this study, we recapitulated the initial mutation needed to evolve citrate utilization in strains isolated from throughout the first 31,500 generations of the history of this population. We found that there was already a slight fitness benefit for this mutation in the original ancestor of the evolution experiment and in other early isolates. However, evolution of citrate utilization was blocked at this point due to competition with other mutations that improved fitness in the original niche. Subsequently, an anti-potentiated genetic background evolved in which it was deleterious to evolve rudimentary citrate utilization. Only later, after further mutations accumulated that restored the benefit of this first-step mutation and the overall rate of adaptation in the population slowed, was citrate utilization likely to evolve. Thus, intense competition and the types of mutations that it favors can lead to short-sighted evolutionary trajectories that hide a stepping stone needed to access a key innovation from many future generations.},
keywords = {Citrate Evolution, Demography and Ecology, Historical Contingency},
pubstate = {published},
tppubtype = {article}
}
Key innovations are disruptive evolutionary events that enable a species to escape constraints and rapidly diversify. After 15 years of the Lenski long-term evolution experiment with Escherichia coli, cells in one of the twelve populations evolved the ability to utilize citrate, an abundant but previously untapped carbon source in the environment. Descendants of these cells became dominant in the population and subsequently diversified as a consequence of invading this vacant niche. Mutations responsible for the appearance of rudimentary citrate utilization and for refining this ability have been characterized. However, the complete nature of the genetic and/or ecological events that set the stage for this key innovation is unknown. In particular, it is unclear why it took so long for citrate utilization to evolve and why it still has evolved in only one of the twelve E. coli populations after 30 years of the Lenski experiment. In this study, we recapitulated the initial mutation needed to evolve citrate utilization in strains isolated from throughout the first 31,500 generations of the history of this population. We found that there was already a slight fitness benefit for this mutation in the original ancestor of the evolution experiment and in other early isolates. However, evolution of citrate utilization was blocked at this point due to competition with other mutations that improved fitness in the original niche. Subsequently, an anti-potentiated genetic background evolved in which it was deleterious to evolve rudimentary citrate utilization. Only later, after further mutations accumulated that restored the benefit of this first-step mutation and the overall rate of adaptation in the population slowed, was citrate utilization likely to evolve. Thus, intense competition and the types of mutations that it favors can lead to short-sighted evolutionary trajectories that hide a stepping stone needed to access a key innovation from many future generations.
Lenski R E; Burnham T C
Experimental evolution of bacteria across 60,000 generations, and what it might mean for economics and human decision-making Journal Article
Journal of Bioeconomics, 20 (1), pp. 107–124, 2018, ISSN: 1387-6996.
Abstract | Links | BibTeX | Altmetric | Tags: Methods and Miscellaneous
@article{Lenski2018,
title = {Experimental evolution of bacteria across 60,000 generations, and what it might mean for economics and human decision-making},
author = {Richard E. Lenski and Terence C. Burnham},
url = {http://link.springer.com/10.1007/s10818-017-9258-7},
doi = {10.1007/s10818-017-9258-7},
issn = {1387-6996},
year = {2018},
date = {2018-04-01},
urldate = {2018-04-01},
journal = {Journal of Bioeconomics},
volume = {20},
number = {1},
pages = {107--124},
publisher = {Springer US},
abstract = {Evolutionary biology and economics are both rich in theory and steeped in data, but they also share challenges including the fact that the systems they seek to understand are, in certain respects, unique and not easily manipulated. Nonetheless, both fields have seen growing efforts to provide experimental approaches to address specific issues. Here, we review some results from a 30-year experiment in which 12 populations of bacteria have been evolving for over 60,000 generations to characterize: (i) the time scale of adaptation to new conditions, (ii) the repeatability of evolutionary changes, and (iii) the benefits and costs of specialization. In each case, we speculate on potential connections and implications of these findings for the field of economics. Moreover, both the bacteria in this experiment and people in modern societies live in novel environments, which leads to an evolutionary mismatch between their genes and environments. Regardless of the value of our speculations, we hope this paper stimulates further interest in pursuing experiments in fields that are often viewed as observational and not amenable to experimentation.},
keywords = {Methods and Miscellaneous},
pubstate = {published},
tppubtype = {article}
}
Evolutionary biology and economics are both rich in theory and steeped in data, but they also share challenges including the fact that the systems they seek to understand are, in certain respects, unique and not easily manipulated. Nonetheless, both fields have seen growing efforts to provide experimental approaches to address specific issues. Here, we review some results from a 30-year experiment in which 12 populations of bacteria have been evolving for over 60,000 generations to characterize: (i) the time scale of adaptation to new conditions, (ii) the repeatability of evolutionary changes, and (iii) the benefits and costs of specialization. In each case, we speculate on potential connections and implications of these findings for the field of economics. Moreover, both the bacteria in this experiment and people in modern societies live in novel environments, which leads to an evolutionary mismatch between their genes and environments. Regardless of the value of our speculations, we hope this paper stimulates further interest in pursuing experiments in fields that are often viewed as observational and not amenable to experimentation.
Peng F; Widmann S; Wünsche A; Duan K; Donovan K A; Dobson R C J; Lenski R E; Cooper T F
Effects of Beneficial Mutations in pykF Gene Vary over Time and across Replicate Populations in a Long-Term Experiment with Bacteria Journal Article
Molecular Biology and Evolution, 35 (1), pp. 202–210, 2018, ISSN: 0737-4038.
Abstract | Links | BibTeX | Altmetric | Tags: Genotypes and Phenotypes, Historical Contingency
@article{Peng2018,
title = {Effects of Beneficial Mutations in \textit{pykF} Gene Vary over Time and across Replicate Populations in a Long-Term Experiment with Bacteria},
author = {Fen Peng and Scott Widmann and Andrea Wünsche and Kristina Duan and Katherine A. Donovan and Renwick C J Dobson and Richard E. Lenski and Tim F. Cooper},
url = {https://academic.oup.com/mbe/article/35/1/202/4562833},
doi = {10.1093/molbev/msx279},
issn = {0737-4038},
year = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {Molecular Biology and Evolution},
volume = {35},
number = {1},
pages = {202--210},
abstract = {The fitness effects of mutations can depend on the genetic backgrounds in which they occur and thereby influence future opportunities for evolving populations. In particular, mutations that fix in a population might change the selective benefit of subsequent mutations, giving rise to historical contingency. We examine these effects by focusing on mutations in a key metabolic gene, \textit{pykF}, that arose independently early in the history of 12 \textit{Escherichia coli} populations during a long-Term evolution experiment. Eight different evolved nonsynonymous mutations conferred similar fitness benefits of ~10% when transferred into the ancestor, and these benefits were greater than the one conferred by a deletion mutation. In contrast, the same mutations had highly variable fitness effects, ranging from ~0% to 25%, in evolved clones isolated from the populations at 20,000 generations. Two mutations that were moved into these evolved clones conferred similar fitness effects in a given clone, but different effects between the clones, indicating epistatic interactions between the evolved \textit{pykF} alleles and the other mutations that had accumulated in each evolved clone. We also measured the fitness effects of six evolved \textit{pykF} alleles in the same populations in which they had fixed, but at seven time points between 0 and 50,000 generations. Variation in fitness effects was high at intermediate time points, and declined to a low level at 50,000 generations, when the mean fitness effect was lowest. Our results demonstrate the importance of genetic context in determining the fitness effects of different beneficial mutations even within the same gene.},
keywords = {Genotypes and Phenotypes, Historical Contingency},
pubstate = {published},
tppubtype = {article}
}
The fitness effects of mutations can depend on the genetic backgrounds in which they occur and thereby influence future opportunities for evolving populations. In particular, mutations that fix in a population might change the selective benefit of subsequent mutations, giving rise to historical contingency. We examine these effects by focusing on mutations in a key metabolic gene, pykF, that arose independently early in the history of 12 Escherichia coli populations during a long-Term evolution experiment. Eight different evolved nonsynonymous mutations conferred similar fitness benefits of ~10% when transferred into the ancestor, and these benefits were greater than the one conferred by a deletion mutation. In contrast, the same mutations had highly variable fitness effects, ranging from ~0% to 25%, in evolved clones isolated from the populations at 20,000 generations. Two mutations that were moved into these evolved clones conferred similar fitness effects in a given clone, but different effects between the clones, indicating epistatic interactions between the evolved pykF alleles and the other mutations that had accumulated in each evolved clone. We also measured the fitness effects of six evolved pykF alleles in the same populations in which they had fixed, but at seven time points between 0 and 50,000 generations. Variation in fitness effects was high at intermediate time points, and declined to a low level at 50,000 generations, when the mean fitness effect was lowest. Our results demonstrate the importance of genetic context in determining the fitness effects of different beneficial mutations even within the same gene.
Maddamsetti R; Lenski R E
PLOS Genetics, 14 (1), pp. e1007199, 2018, ISSN: 1553-7404.
Abstract | Links | BibTeX | Altmetric | Tags: Descendant Experiments, Genome Evolution
@article{Maddamsetti2018,
title = {Analysis of bacterial genomes from an evolution experiment with horizontal gene transfer shows that recombination can sometimes overwhelm selection},
author = {Rohan Maddamsetti and Richard E. Lenski},
editor = {Ivan Matic},
url = {https://dx.plos.org/10.1371/journal.pgen.1007199},
doi = {10.1371/journal.pgen.1007199},
issn = {1553-7404},
year = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {PLOS Genetics},
volume = {14},
number = {1},
pages = {e1007199},
abstract = {Few experimental studies have examined the role that sexual recombination plays in bacterial evolution, including the effects of horizontal gene transfer on genome structure. To address this limitation, we analyzed genomes from an experiment in which \textit{Escherichia coli} K-12 Hfr (high frequency recombination) donors were periodically introduced into 12 evolving populations of \textit{E. coli} B and allowed to conjugate repeatedly over the course of 1000 generations. Previous analyses of the evolved strains from this experiment showed that recombination did not accelerate adaptation, despite increasing genetic variation relative to asexual controls. However, the resolution in that previous work was limited to only a few genetic markers. We sought to clarify and understand these puzzling results by sequencing complete genomes from each population. The effects of recombination were highly variable: one lineage was mostly derived from the donors, while another acquired almost no donor DNA. In most lineages, some regions showed repeated introgression and others almost none. Regions with high introgression tended to be near the donors' origin of transfer sites. To determine whether introgressed alleles imposed a genetic load, we extended the experiment for 200 generations without recombination and sequenced whole-population samples. Beneficial alleles in the recipient populations were occasionally driven extinct by maladaptive donor-derived alleles. On balance, our analyses indicate that the plasmid-mediated recombination was sufficiently frequent to drive donor alleles to fixation without providing much, if any, selective advantage.},
keywords = {Descendant Experiments, Genome Evolution},
pubstate = {published},
tppubtype = {article}
}
Few experimental studies have examined the role that sexual recombination plays in bacterial evolution, including the effects of horizontal gene transfer on genome structure. To address this limitation, we analyzed genomes from an experiment in which Escherichia coli K-12 Hfr (high frequency recombination) donors were periodically introduced into 12 evolving populations of E. coli B and allowed to conjugate repeatedly over the course of 1000 generations. Previous analyses of the evolved strains from this experiment showed that recombination did not accelerate adaptation, despite increasing genetic variation relative to asexual controls. However, the resolution in that previous work was limited to only a few genetic markers. We sought to clarify and understand these puzzling results by sequencing complete genomes from each population. The effects of recombination were highly variable: one lineage was mostly derived from the donors, while another acquired almost no donor DNA. In most lineages, some regions showed repeated introgression and others almost none. Regions with high introgression tended to be near the donors' origin of transfer sites. To determine whether introgressed alleles imposed a genetic load, we extended the experiment for 200 generations without recombination and sequenced whole-population samples. Beneficial alleles in the recipient populations were occasionally driven extinct by maladaptive donor-derived alleles. On balance, our analyses indicate that the plasmid-mediated recombination was sufficiently frequent to drive donor alleles to fixation without providing much, if any, selective advantage.
2017
Lenski R E
What is adaptation by natural selection? Perspectives of an experimental microbiologist Journal Article
PLOS Genetics, 13 (4), pp. e1006668, 2017, ISSN: 1553-7404.
Abstract | Links | BibTeX | Altmetric | Tags: Review Articles
@article{Lenski2017,
title = {What is adaptation by natural selection? Perspectives of an experimental microbiologist},
author = {Richard E. Lenski},
editor = {W. Ford Doolittle},
url = {https://dx.plos.org/10.1371/journal.pgen.1006668},
doi = {10.1371/journal.pgen.1006668},
issn = {1553-7404},
year = {2017},
date = {2017-04-01},
urldate = {2017-04-01},
journal = {PLOS Genetics},
volume = {13},
number = {4},
pages = {e1006668},
abstract = {Use of at least three potent antiretroviral agents has become the standard of care in the management of HIV infection. The potential toxicities associated with highly active antiretroviral therapy (HAART) however, may limit a patient's ability to adhere to and tolerate these agents. Although a comprehensive discussion of all toxicities associated with HAART is beyond the scope of this article, selected short-term and long-term significant toxicities will be reviewed. Short-term toxicities that will be discussed include abacavir-induced hypersensitivity reactions, efavirenz-associated central nervous system side effects and rash associated with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitor (PI) amprenavir. Several long-term toxicities associated with the nucleoside reverse transcriptase inhibitors (NRTIs) are hypothesized to be due to mitochondrial toxicity. These toxicities include myositis and lactic acidosis with hepatic steatosis, pancreatitis and peripheral neuropathy. Some experts also hypothesize that mitochondrial toxicity is responsible for the lipodystrophy syndrome, which includes hyperglycemia, abnormal fat redistribution and dyslipidemia. Finally, indinavir-associated nephrolithiasis, which may present with either short term or long term use will be discussed. This article will provide the practicing pharmacist with a review of these significant toxicities, the implicated agents, incidence, usual clinical presentation, and recommendations for management.},
keywords = {Review Articles},
pubstate = {published},
tppubtype = {article}
}
Use of at least three potent antiretroviral agents has become the standard of care in the management of HIV infection. The potential toxicities associated with highly active antiretroviral therapy (HAART) however, may limit a patient's ability to adhere to and tolerate these agents. Although a comprehensive discussion of all toxicities associated with HAART is beyond the scope of this article, selected short-term and long-term significant toxicities will be reviewed. Short-term toxicities that will be discussed include abacavir-induced hypersensitivity reactions, efavirenz-associated central nervous system side effects and rash associated with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitor (PI) amprenavir. Several long-term toxicities associated with the nucleoside reverse transcriptase inhibitors (NRTIs) are hypothesized to be due to mitochondrial toxicity. These toxicities include myositis and lactic acidosis with hepatic steatosis, pancreatitis and peripheral neuropathy. Some experts also hypothesize that mitochondrial toxicity is responsible for the lipodystrophy syndrome, which includes hyperglycemia, abnormal fat redistribution and dyslipidemia. Finally, indinavir-associated nephrolithiasis, which may present with either short term or long term use will be discussed. This article will provide the practicing pharmacist with a review of these significant toxicities, the implicated agents, incidence, usual clinical presentation, and recommendations for management.
Deatherage D E; Kepner J L; Bennett A F; Lenski R E; Barrick J E
Specificity of genome evolution in experimental populations of Escherichia coli evolved at different temperatures Journal Article
Proceedings of the National Academy of Sciences, 114 (10), pp. E1904–E1912, 2017, ISSN: 0027-8424.
Abstract | Links | BibTeX | Altmetric | Tags: Descendant Experiments
@article{Deatherage2017,
title = {Specificity of genome evolution in experimental populations of \textit{Escherichia coli} evolved at different temperatures},
author = {Daniel E. Deatherage and Jamie L. Kepner and Albert F. Bennett and Richard E. Lenski and Jeffrey E. Barrick},
url = {http://www.pnas.org/lookup/doi/10.1073/pnas.1616132114},
doi = {10.1073/pnas.1616132114},
issn = {0027-8424},
year = {2017},
date = {2017-03-01},
urldate = {2017-03-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {114},
number = {10},
pages = {E1904--E1912},
abstract = {Isolated populations derived from a common ancestor are expected to diverge genetically and phenotypically as they adapt to different local environments. To examine this process, 30 populations of \textit{Escherichia coli} were evolved for 2,000 generations, with six in each of five different thermal regimes: constant 20 °C, 32 °C, 37 °C, 42 °C, and daily alternations between 32 °C and 42 °C. Here, we sequenced the genomes of one endpoint clone from each population to test whether the history of adaptation in different thermal regimes was evident at the genomic level. The evolved strains had accumulated ∼5.3 mutations, on average, and exhibited distinct signatures of adaptation to the different environments. On average, two strains that evolved under the same regime exhibited ∼17% overlap in which genes were mutated, whereas pairs that evolved under different conditions shared only ∼4%. For example, all six strains evolved at 32 °C had mutations in nadR , whereas none of the other 24 strains did. However, a population evolved at 37 °C for an additional 18,000 generations eventually accumulated mutations in the signature genes strongly associated with adaptation to the other temperature regimes. Two mutations that arose in one temperature treatment tended to be beneficial when tested in the others, although less so than in the regime in which they evolved. These findings demonstrate that genomic signatures of adaptation can be highly specific, even with respect to subtle environmental differences, but that this imprint may become obscured over longer timescales as populations continue to change and adapt to the shared features of their environments.},
keywords = {Descendant Experiments},
pubstate = {published},
tppubtype = {article}
}
Isolated populations derived from a common ancestor are expected to diverge genetically and phenotypically as they adapt to different local environments. To examine this process, 30 populations of Escherichia coli were evolved for 2,000 generations, with six in each of five different thermal regimes: constant 20 °C, 32 °C, 37 °C, 42 °C, and daily alternations between 32 °C and 42 °C. Here, we sequenced the genomes of one endpoint clone from each population to test whether the history of adaptation in different thermal regimes was evident at the genomic level. The evolved strains had accumulated ∼5.3 mutations, on average, and exhibited distinct signatures of adaptation to the different environments. On average, two strains that evolved under the same regime exhibited ∼17% overlap in which genes were mutated, whereas pairs that evolved under different conditions shared only ∼4%. For example, all six strains evolved at 32 °C had mutations in nadR , whereas none of the other 24 strains did. However, a population evolved at 37 °C for an additional 18,000 generations eventually accumulated mutations in the signature genes strongly associated with adaptation to the other temperature regimes. Two mutations that arose in one temperature treatment tended to be beneficial when tested in the others, although less so than in the regime in which they evolved. These findings demonstrate that genomic signatures of adaptation can be highly specific, even with respect to subtle environmental differences, but that this imprint may become obscured over longer timescales as populations continue to change and adapt to the shared features of their environments.
Good B H; McDonald M J; Barrick J E; Lenski R E; Desai M M
The dynamics of molecular evolution over 60,000 generations Journal Article
Nature, 551 (7678), pp. 45–50, 2017, ISSN: 14764687.
Abstract | Links | BibTeX | Altmetric | Tags: Demography and Ecology, Genome Evolution, Historical Contingency, Mutation Rates, Parallelism and Divergence
@article{Good2017,
title = {The dynamics of molecular evolution over 60,000 generations},
author = {Benjamin H. Good and Michael J. McDonald and Jeffrey E. Barrick and Richard E. Lenski and Michael M. Desai},
url = {http://dx.doi.org/10.1038/nature24287},
doi = {10.1038/nature24287},
issn = {14764687},
year = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Nature},
volume = {551},
number = {7678},
pages = {45--50},
publisher = {Nature Publishing Group},
abstract = {The outcomes of evolution are determined by a stochastic dynamical process that governs how mutations arise and spread through a population. However, it is difficult to observe these dynamics directly over long periods and across entire genomes. Here we analyse the dynamics of molecular evolution in twelve experimental populations of \textit{Escherichia coli}, using whole-genome metagenomic sequencing at five hundred-generation intervals through sixty thousand generations. Although the rate of fitness gain declines over time, molecular evolution is characterized by signatures of rapid adaptation throughout the duration of the experiment, with multiple beneficial variants simultaneously competing for dominance in each population. Interactions between ecological and evolutionary processes play an important role, as long-term quasi-stable coexistence arises spontaneously in most populations, and evolution continues within each clade. We also present evidence that the targets of natural selection change over time, as epistasis and historical contingency alter the strength of selection on different genes. Together, these results show that long-term adaptation to a constant environment can be a more complex and dynamic process than is often assumed.},
keywords = {Demography and Ecology, Genome Evolution, Historical Contingency, Mutation Rates, Parallelism and Divergence},
pubstate = {published},
tppubtype = {article}
}
The outcomes of evolution are determined by a stochastic dynamical process that governs how mutations arise and spread through a population. However, it is difficult to observe these dynamics directly over long periods and across entire genomes. Here we analyse the dynamics of molecular evolution in twelve experimental populations of Escherichia coli, using whole-genome metagenomic sequencing at five hundred-generation intervals through sixty thousand generations. Although the rate of fitness gain declines over time, molecular evolution is characterized by signatures of rapid adaptation throughout the duration of the experiment, with multiple beneficial variants simultaneously competing for dominance in each population. Interactions between ecological and evolutionary processes play an important role, as long-term quasi-stable coexistence arises spontaneously in most populations, and evolution continues within each clade. We also present evidence that the targets of natural selection change over time, as epistasis and historical contingency alter the strength of selection on different genes. Together, these results show that long-term adaptation to a constant environment can be a more complex and dynamic process than is often assumed.
