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Nature Ecology & Evolution Feb 2022Prochlorococcus are the most abundant free-living photosynthetic carbon-fixing organisms in the ocean. Prochlorococcus show small genome sizes, low genomic G+C content,...
Prochlorococcus are the most abundant free-living photosynthetic carbon-fixing organisms in the ocean. Prochlorococcus show small genome sizes, low genomic G+C content, reduced DNA repair gene pool and fast evolutionary rates, which are typical features of endosymbiotic bacteria. Nevertheless, their evolutionary mechanisms are believed to be different. Evolution of endosymbiotic bacteria is dominated by genetic drift owing to repeated population bottlenecks, whereas Prochlorococcus are postulated to have extremely large effective population sizes (N) and thus drift has rarely been considered. However, accurately extrapolating N requires measuring an unbiased global mutation rate through mutation accumulation, which is challenging for Prochlorococcus. Here, we managed this experiment over 1,065 days using Prochlorococcus marinus AS9601, sequenced genomes of 141 mutant lines and determined its mutation rate to be 3.50 × 10 per site per generation. Extrapolating N additionally requires identifying population boundaries, which we defined using PopCOGenT and over 400 genomes related to AS9601. Accordingly, we calculated its N to be 1.68 × 10, which is only reasonably greater than that of endosymbiotic bacteria but surprisingly smaller than that of many free-living bacteria extrapolated using the same approach. Our results therefore suggest that genetic drift is a key driver of Prochlorococcus evolution.
Topics: Evolution, Molecular; Genome, Bacterial; Mutation Rate; Population Density; Prochlorococcus
PubMed: 34949817
DOI: 10.1038/s41559-021-01591-0 -
G3 (Bethesda, Md.) Mar 2023Archaea are a major part of Earth's microbiota and extremely diverse. Yet, we know very little about the process of mutation that drives such diversification. To expand...
Archaea are a major part of Earth's microbiota and extremely diverse. Yet, we know very little about the process of mutation that drives such diversification. To expand beyond previous work with the moderate halophilic archaeal species Haloferax volcanii, we performed a mutation-accumulation experiment followed by whole-genome sequencing in the extremely halophilic archaeon Halobacterium salinarum. Although Hfx. volcanii and Hbt. salinarum have different salt requirements, both species have highly polyploid genomes and similar GC content. We accumulated mutations for an average of 1250 generations in 67 mutation accumulation lines of Hbt. salinarum, and revealed 84 single-base substitutions and 10 insertion-deletion mutations. The estimated base-substitution mutation rate of 3.99 × 10-10 per site per generation or 1.0 × 10-3 per genome per generation in Hbt. salinarum is similar to that reported for Hfx. volcanii (1.2 × 10-3 per genome per generation), but the genome-wide insertion-deletion rate and spectrum of mutations are somewhat dissimilar in these archaeal species. The spectra of spontaneous mutations were AT biased in both archaea, but they differed in significant ways that may be related to differences in the fidelity of DNA replication/repair mechanisms or a simple result of the different salt concentrations.
Topics: Mutation Rate; Haloferax volcanii; Mutation; DNA Repair; Archaeal Proteins; Archaea
PubMed: 36519377
DOI: 10.1093/g3journal/jkac303 -
Proceedings of the National Academy of... May 2023Direct reciprocity is a powerful mechanism for the evolution of cooperation based on repeated interactions between the same individuals. But high levels of cooperation...
Direct reciprocity is a powerful mechanism for the evolution of cooperation based on repeated interactions between the same individuals. But high levels of cooperation evolve only if the benefit-to-cost ratio exceeds a certain threshold that depends on memory length. For the best-explored case of one-round memory, that threshold is two. Here, we report that intermediate mutation rates lead to high levels of cooperation, even if the benefit-to-cost ratio is only marginally above one, and even if individuals only use a minimum of past information. This surprising observation is caused by two effects. First, mutation generates diversity which undermines the evolutionary stability of defectors. Second, mutation leads to diverse communities of cooperators that are more resilient than homogeneous ones. This finding is relevant because many real-world opportunities for cooperation have small benefit-to-cost ratios, which are between one and two, and we describe how direct reciprocity can attain cooperation in such settings. Our result can be interpreted as showing that diversity, rather than uniformity, promotes evolution of cooperation.
Topics: Humans; Cooperative Behavior; Game Theory; Biological Evolution; Mutation; Mutation Rate
PubMed: 37155877
DOI: 10.1073/pnas.2221080120 -
Nature Genetics Jul 2022Compelling evidence shows that cancer persister cells represent a major limit to the long-term efficacy of targeted therapies. However, the phenotype and population...
Compelling evidence shows that cancer persister cells represent a major limit to the long-term efficacy of targeted therapies. However, the phenotype and population dynamics of cancer persister cells remain unclear. We developed a quantitative framework to study persisters by combining experimental characterization and mathematical modeling. We found that, in colorectal cancer, a fraction of persisters slowly replicates. Clinically approved targeted therapies induce a switch to drug-tolerant persisters and a temporary 7- to 50-fold increase of their mutation rate, thus increasing the number of persister-derived resistant cells. These findings reveal that treatment may influence persistence and mutability in cancer cells and pinpoint inhibition of error-prone DNA polymerases as a strategy to restrict tumor recurrence.
Topics: Anti-Bacterial Agents; Colorectal Neoplasms; Humans; Mutation Rate; Population Dynamics
PubMed: 35817983
DOI: 10.1038/s41588-022-01105-z -
Microbiology (Reading, England) May 2023Natural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating...
Natural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating this genetic variation: to become evolutionarily successful, adaptive mutants must not only reach fixation, but also emerge in the first place, i.e. have a high enough mutation rate. Here, we use numerical simulations to investigate how mutational biases impact our ability to observe rare mutational pathways in the laboratory and to predict outcomes in experimental evolution. We show that unevenness in the rates at which mutational pathways produce adaptive mutants means that most experimental studies lack power to directly observe the full range of adaptive mutations. Modelling mutation rates as a distribution, we show that a substantially larger target size ensures that a pathway mutates more commonly. Therefore, we predict that commonly mutated pathways are conserved between closely related species, but not rarely mutated pathways. This approach formalizes our proposal that most mutations have a lower mutation rate than the average mutation rate measured experimentally. We suggest that the extent of genetic variation is overestimated when based on the average mutation rate.
Topics: Mutation Rate; Mutation; Selection, Genetic
PubMed: 37134005
DOI: 10.1099/mic.0.001323 -
Proceedings of the National Academy of... Oct 2019Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the...
Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multimutation leaps, that is, several mutations occurring simultaneously, within a single generation in 1 genome, and being fixed all together in the evolving population. The results indicate that, for typical, empirically observed combinations of the parameters of the evolutionary process, namely, effective population size, mutation rate, and distribution of selection coefficients of mutations, the probability of a multimutation leap is low, and accordingly the contribution of such leaps is minor at best. However, we show that, taking sign epistasis into account, leaps could become an important factor of evolution in cases of substantially elevated mutation rates, such as stress-induced mutagenesis in microbes. We hypothesize that stress-induced mutagenesis is an evolvable adaptive strategy.
Topics: Epistasis, Genetic; Evolution, Molecular; Feasibility Studies; Genetic Fitness; Genome; Models, Theoretical; Mutagenesis; Mutation; Mutation Rate; Population Density
PubMed: 31570621
DOI: 10.1073/pnas.1909031116 -
Biomolecules Mar 2023The yeast petite mutant was first discovered in the yeast , which shows growth stress due to defects in genes encoding the respiratory chain. In a previous study, we...
The yeast petite mutant was first discovered in the yeast , which shows growth stress due to defects in genes encoding the respiratory chain. In a previous study, we described that deletion of the nuclear-encoded gene leads to mitochondrial genome (mtDNA) loss and the petite phenotype, which can be rescued by acquiring mutations. The strain showed an elevated SNV (single nucleotide variant) rate, suggesting genome instability occurred during the crisis of mtDNA loss. However, the genome-wide mutation landscape and mutational signatures of mitochondrial dysfunction are unknown. In this study we profiled the mutation spectra in yeast strains with the genotype combination of and in their wildtype and mutated status, along with the wildtype and cytoplasmic petite rho0 strains as controls. In addition to the previously described elevated SNV rate, we found the INDEL (insertion/deletion) rate also increased in the strain, reinforcing the occurrence of genome instability. Notably, although both are petites, the and rho0 strains exhibited different INDEL rates and transition/transversion ratios, suggesting differences in the mutational signatures underlying these two types of petites. Interestingly, the petite-related mutagenesis effect disappeared when suppressor mutations were acquired, suggesting a cost-effective mechanism for restoring both fitness and genome stability. Taken together, we present an unbiased genome-wide characterization of the mutation rates and spectra of yeast strains with respiratory deficiency, which provides valuable insights into the impact of respiratory deficiency on genome instability.
Topics: Humans; Saccharomyces cerevisiae; Mutation Rate; Mutation; Genomic Instability; DNA, Mitochondrial
PubMed: 36979436
DOI: 10.3390/biom13030501 -
BMC Ecology and Evolution May 2021The formation of the Isthmus of Panama and final closure of the Central American Seaway (CAS) provides an independent calibration point for examining the rate of DNA...
BACKGROUND
The formation of the Isthmus of Panama and final closure of the Central American Seaway (CAS) provides an independent calibration point for examining the rate of DNA substitutions. This vicariant event has been widely used to estimate the substitution rate across mitochondrial genomes and to date evolutionary events in other taxonomic groups. Nuclear sequence data is increasingly being used to complement mitochondrial datasets for phylogenetic and evolutionary investigations; these studies would benefit from information regarding the rate and pattern of DNA substitutions derived from the nuclear genome.
RESULTS
To estimate the genome-wide neutral mutation rate (µ), genotype-by-sequencing (GBS) datasets were generated for three transisthmian species pairs in Alpheus snapping shrimp. A range of bioinformatic filtering parameters were evaluated in order to minimize potential bias in mutation rate estimates that may result from SNP filtering. Using a Bayesian coalescent approach (G-PhoCS) applied to 44,960 GBS loci, we estimated µ to be 2.64E-9 substitutions/site/year, when calibrated with the closure of the CAS at 3 Ma. Post-divergence gene flow was detected in one species pair. Failure to account for this post-split migration inflates our substitution rate estimates, emphasizing the importance of demographic methods that can accommodate gene flow.
CONCLUSIONS
Results from our study, both parameter estimates and bioinformatic explorations, have broad-ranging implications for phylogeographic studies in other non-model taxa using reduced representation datasets. Our best estimate of µ that accounts for coalescent and demographic processes is remarkably similar to experimentally derived mutation rates in model arthropod systems. These results contradicted recent suggestions that the closure of the Isthmus was completed much earlier (around 10 Ma), as mutation rates based on an early calibration resulted in uncharacteristically low genomic mutation rates. Also, stricter filtering parameters resulted in biased datasets that generated lower mutation rate estimates and influenced demographic parameters, serving as a cautionary tale for the adherence to conservative bioinformatic strategies when generating reduced-representation datasets at the species level. To our knowledge this is the first use of transisthmian species pairs to calibrate the rate of molecular evolution from GBS data.
Topics: Animals; Bayes Theorem; Decapoda; Mutation Rate; Panama; Phylogeny
PubMed: 34049492
DOI: 10.1186/s12862-021-01836-3 -
Nature Genetics Nov 2020Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from...
Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.
Topics: Animals; Carcinogenesis; Carcinogens; DNA Mutational Analysis; Environmental Pollutants; Female; Genome; Humans; Male; Mice; Mutation; Mutation Rate; Propane; Species Specificity
PubMed: 32989322
DOI: 10.1038/s41588-020-0692-4 -
Legal Medicine (Tokyo, Japan) Sep 2022The short tandem repeats (STRs) or microsatellites are used for paternity testing and these sequences mutate more rapidlythanbulkDNAsequences. A total of 746 paternity...
The short tandem repeats (STRs) or microsatellites are used for paternity testing and these sequences mutate more rapidlythanbulkDNAsequences. A total of 746 paternity cases were analysed to understand the mutation rate of 21 autosomal STR loci. We identified 41 mutations in 11 STR Loci with a maximum at SE33. No mutations occurred in the remaining 10 STR loci. The overall average mutation rate was estimated as 0.004523 and the estimated locus-specific mutation rate varied between 0.001214 and 0.016990. Among these 90.24% was accounted for single-step mutation, 2.44% for two steps, and 7.32 % for three or muti steps. The obtained data is crucial and could be helpful for ensuring the accuracy of DNA testing and interpretation.
Topics: DNA; Humans; Microsatellite Repeats; Mutation; Mutation Rate; Paternity
PubMed: 35526480
DOI: 10.1016/j.legalmed.2022.102080