Title: Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli
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 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. more »« less
Maddamsetti, Rohan
(, Genome Biology and Evolution)
Golding, Brian
(Ed.)
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 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.
Sherer, Nicholas A.; Kuhlman, Thomas E.
(, G3: Genes|Genomes|Genetics)
The mutation rate and mutations' effects on fitness are crucial to evolution. Mutation rates are under selection due to linkage between mutation rate modifiers and mutations' effects on fitness. The linkage between a higher mutation rate and more beneficial mutations selects for higher mutation rates, while the linkage between a higher mutation rate and more deleterious mutations selects for lower mutation rates. The net direction of selection on mutations rates depends on the fitness landscape, and a great deal of work has elucidated the fitness landscapes of mutations. However, tests of the effect of varying a mutation rate on evolution in a single organism in a single environment have been difficult. This has been studied using strains of antimutators and mutators, but these strains may differ in additional ways and typically do not allow for continuous variation of the mutation rate. To help investigate the effects of the mutation rate on evolution, we have genetically engineered a strain of E. coli with a point mutation rate that can be smoothly varied over two orders of magnitude. We did this by engineering a strain with inducible control of the mismatch repair proteins MutH and MutL. We used this strain in an approximately 350 generation evolution experiment with controlled variation of the mutation rate. We confirmed the construct and the mutation rate were stable over this time. Sequencing evolved strains revealed a higher number of single nucleotide polymorphisms at higher mutations rates, likely due to either the beneficial effects of these mutations or their linkage to beneficial mutations.
Mulvey, Kathryn; Brosnan, Katherine; Galvin, Mackenzie; Mohr, Sydney; Muldowney, Lauren; Oser, Molly; Williams, Laura E.
(, Applied and Environmental Microbiology)
Villanueva, Laura
(Ed.)
ABSTRACT Experimental evolution provides a powerful tool for examining how Bdellovibrio evolves in response to unique selective pressures associated with its predatory lifestyle. We tested how Bdellovibrio sp. NC01 adapts to long-term coculture with Pseudomonas sp. NC02, which is less susceptible to predation compared to other Gram-negative bacteria. Analyzing six replicate Bdellovibrio populations across six time points spanning 40 passages and 2,880 h of coculture, we detected 30 to 40 new mutations in each population that exceeded a frequency of 5%. Nonsynonymous substitutions were the most abundant type of new mutation, followed by small indels and synonymous substitutions. After completing the final passage, we detected 20 high-frequency (>75%) mutations across all six evolved Bdellovibrio populations. Eighteen of these alter protein sequences, and most increased in frequency rapidly. Four genes acquired a high-frequency mutation in two or more evolved Bdellovibrio populations, reflecting parallel evolution and positive selection. The genes encode a sodium/phosphate cotransporter family protein (Bd2221), a metallophosphoesterase (Bd0054), a TonB family protein (Bd0396), and a hypothetical protein (Bd1601). Tested prey range and predation efficiency phenotypes did not differ significantly between evolved Bdellovibrio populations and the ancestor; however, all six evolved Bdellovibrio populations demonstrated enhanced starvation survival compared to the ancestor. These results suggest that, instead of evolving improved killing of Pseudomonas sp. NC02, Bdellovibrio evolved to better withstand nutrient limitation in the presence of this prey strain. The mutations identified here point to genes and functions that may be important for Bdellovibrio adaptation to the different selective pressures of long-term coculture with Pseudomonas . IMPORTANCE Bdellovibrio attack and kill Gram-negative bacteria, including drug-resistant pathogens of animals and plants. This lifestyle is unusual among bacteria, and it imposes unique selective pressures on Bdellovibrio . Determining how Bdellovibrio evolve in response to these pressures is valuable for understanding the mechanisms that govern predation. We applied experimental evolution to test how Bdellovibrio sp. NC01 evolved in response to long-term coculture with a single Pseudomonas strain, which NC01 can kill, but with low efficiency. Our experimental design imposed different selective pressures on the predatory bacteria and tracked the evolutionary trajectories of replicate Bdellovibrio populations. Using genome sequencing, we identified Bdellovibrio genes that acquired high-frequency mutations in two or more populations. Using phenotype assays, we determined that evolved Bdellovibrio populations did not improve their ability to kill Pseudomonas , but rather are better able to survive starvation. Overall, our results point to functions that may be important for Bdellovibrio adaptation.
Izutsu, Minako; Lenski, Richard E.
(, Frontiers in Ecology and Evolution)
Experimental evolution is an approach that allows researchers to study organisms as they evolve in controlled environments. Despite the growing popularity of this approach, there are conceptual gaps among projects that use different experimental designs. One such gap concerns the contributions to adaptation of genetic variation present at the start of an experiment and that of new mutations that arise during an experiment. The primary source of genetic variation has historically depended largely on the study organisms. In the long-term evolution experiment (LTEE) using Escherichia coli , for example, each population started from a single haploid cell, and therefore, adaptation depended entirely on new mutations. Most other microbial evolution experiments have followed the same strategy. By contrast, evolution experiments using multicellular, sexually reproducing organisms typically start with preexisting variation that fuels the response to selection. New mutations may also come into play in later generations of these experiments, but it is generally difficult to quantify their contribution in these studies. Here, we performed an experiment using E. coli to compare the contributions of initial genetic variation and new mutations to adaptation in a new environment. Our experiment had four treatments that varied in their starting diversity, with 18 populations in each treatment. One treatment depended entirely on new mutations, while the other three began with mixtures of clones, whole-population samples, or mixtures of whole-population samples from the LTEE. We tracked a genetic marker associated with different founders in two treatments. These data revealed significant variation in fitness among the founders, and that variation impacted evolution in the early generations of our experiment. However, there were no differences in fitness among the treatments after 500 or 2,000 generations in the new environment, despite the variation in fitness among the founders. These results indicate that new mutations quickly dominated, and eventually they contributed more to adaptation than did the initial variation. Our study thus shows that preexisting genetic variation can have a strong impact on early evolution in a new environment, but new beneficial mutations may contribute more to later evolution and can even drive some initially beneficial variants to extinction.
Favate, John S; Liang, Shun; Cope, Alexander L; Yadavalli, Srujana Samhita; Shah, Premal
(, eLife)
Organisms can adapt to an environment by taking multiple mutational paths. This redundancy at the genetic level, where many mutations have similar phenotypic and fitness effects, can make untangling the molecular mechanisms of complex adaptations difficult. Here we use the E. coli long-term evolution experiment (LTEE) as a model to address this challenge. To understand how different genomic changes could lead to parallel fitness gains, we characterize the landscape of transcriptional and translational changes across 12 replicate populations evolving in parallel for 50,000 generations. By quantifying absolute changes in mRNA abundances, we show that not only do all evolved lines have more mRNAs but that this increase in mRNA abundance scales with cell size. We also find that despite few shared mutations at the genetic level, clones from replicate populations in the LTEE are remarkably similar in their gene expression patterns at both the transcriptional and translational levels. Furthermore, we show that the majority of the expression changes are due to changes at the transcriptional level with very few translational changes. Finally, we show how mutations in transcriptional regulators lead to consistent and parallel changes in the expression levels of downstream genes. These results deepen our understanding of the molecular mechanisms underlying complex adaptations and provide insights into the repeatability of evolution.
Maddamsetti, Rohan, and Grant, Nkrumah A. Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli. Retrieved from https://par.nsf.gov/biblio/10272492. Genome Biology and Evolution 12.9 Web. doi:10.1093/gbe/evaa178.
Maddamsetti, Rohan, & Grant, Nkrumah A. Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli. Genome Biology and Evolution, 12 (9). Retrieved from https://par.nsf.gov/biblio/10272492. https://doi.org/10.1093/gbe/evaa178
Maddamsetti, Rohan, and Grant, Nkrumah A.
"Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli". Genome Biology and Evolution 12 (9). Country unknown/Code not available. https://doi.org/10.1093/gbe/evaa178.https://par.nsf.gov/biblio/10272492.
@article{osti_10272492,
place = {Country unknown/Code not available},
title = {Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli},
url = {https://par.nsf.gov/biblio/10272492},
DOI = {10.1093/gbe/evaa178},
abstractNote = {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 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.},
journal = {Genome Biology and Evolution},
volume = {12},
number = {9},
author = {Maddamsetti, Rohan and Grant, Nkrumah A},
editor = {Zhang, George}
}
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