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Adaptive laboratory evolution—Principles and applications for biotechnology
Open accessAbstract
Adaptive laboratory evolution is a frequent method in biological studies to gain insights into the basic mechanisms of molecular evolution and adaptive changes that accumulate in microbial populations during long term selection under specified growth conditions. Although regularly performed for more than 25 years, the advent of transcript and cheap next-generation sequencing technologies has resulted in many recent studies, which successfully applied this technique in order to engineer microbial cells for biotechnological applications. Adaptive laboratory evolution has some major benefits as compared with classical genetic engineering but also some inherent limitations. However, recent studies show how some of the limitations may be overcome in order to successfully incorporate adaptive laboratory evolution in microbial cell factory design. Over the last two decades important insights into nutrient and stress metabolism of relevant model species were acquired, whereas some other aspects such as niche-specific differences of non-conventional cell factories are not completely understood. Altogether the current status and its future perspectives highlight the importance and potential of adaptive laboratory evolution as approach in biotechnological engineering.
Overview
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Written from the paper’s full text.
TL;DR
Adaptive laboratory evolution (ALE) is a long-term selection approach that can improve microbial growth, stress tolerance, and biotechnologically relevant phenotypes, often complementing classical genetic engineering. This review summarizes principles, selection methods, mutation types, trade-offs, and applications across bacteria and yeasts, while noting limitations such as unknown evolved genotypes, trade-offs, and limited data for non-conventional hosts.
Key findings
- Typical ALE experiments run for about 100–2000 generations over weeks to months; within 100–500 generations, fitness increases of up to 50–100% can be achieved, while an extreme case reached up to 1000% improvement in iron reduction rate for *Geobacter sulfurreducens* after 24 months.
- Across ALE studies, SNPs accounted for 61% of observed genetic changes, deletions approximately 29%, insertions 7%, and insertion-sequence movements 3%; the Lenski *E. coli* experiment exceeds 50,000 generations.
- ALE can improve nutrient utilization and stress resistance, but evolved phenotypes often show trade-offs or cross-protection depending on selection conditions; for example, ethanol tolerance in *E. coli* came at the cost of decreased acid resistance, while n-butanol tolerance was weakly compatible with oxidative stress.
- Large-scale transcriptional rearrangements, gene amplifications, and regulatory mutations are common; epistasis is a major factor, and different evolutionary paths can lead to phenotypic convergence.
Methods
- This is a review article, not a primary experimental study; it synthesizes principles and applications of ALE for biotechnology.
- It draws on published ALE experiments with bacteria and yeasts, summarized in Table 1 and Table 2, which list species/strain, selection environment, selection time, and references.
- The main analysis is a narrative synthesis covering laboratory selection methods, mutation types, nutrient and environmental stress adaptation, evolutionary trade-offs and cross-protection, non-conventional hosts, and future directions.
Limitations
- The paper states that ALE has inherent limitations: evolved strains have unknown genotypes, risking hitchhiking of unfavorable mutations; selection for one condition often causes trade-offs in others; efficient evolutionary engineering of industrial *S. cerevisiae* may be limited by polyploidy; and computational models cannot yet replace trial-and-error laboratory experiments.
- The paper states that non-conventional host organisms are understudied, with limited physiological data and niche-specific differences not completely understood.
- Evident from the text: as a review, it does not perform a systematic search or meta-analysis, and some entries in Tables 1 and 2 report “nd” for selection time, indicating incomplete data in the summarized literature.
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Figures
![Figure 1 Adaptive laboratory evolution (ALE). ALE can be performed in the laboratory by (a) sequential serial passages in shake flasks, where nutrients will not be limited and certain growth parameters can heavily fluctuate. (b) Alternatively, chemostat cultures can be applied, where one nutritional component is typically limited and cell density can be much higher than in shake flasks. Additionally, cell density and environmental conditions can be kept constant and more complex cultivation strategies can be implemented. (c) The increase of fitness during laboratory evolution experiments is fast in the first stage but generally slows down during prolonged selection, whereas the number of mutations is steadily increasing; however network complexity leads to a decreasing beneficial effect of additional mutations. [36,67]. (d) Mutations that are usually identified in ALE studies. Single nucleotide polymorphisms (SNPs), smaller insertions and deletions (indels) and larger deletions and insertions contribute to genetic and gene regulatory changes and fitness changes during the selection for improved phenotypes.](/paper-figures/5480462933364ae8b4e83ffdc57af598/adaptive-laboratory-evolutionprinciples-and-applications-for-biotechnology-figure-1.jpg)
Verification
Claims the paper makes
134 Not checked yet · 13 Own interpretation · 7 No basis given · 2 Own result · 1 Couldn’t confirm · accuracy not yet measured
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In the paper
“Other biotechnological processes, such as recombinant protein production and metabolite co-production in microbial cells, are coupled to microbial growth [56].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Laboratory selection methods
What the sources say
- Could not verifycites [56] sourceExperimental — accuracy not yet measured
The Methods and Results and Discussion passages address E. coli evolution, gene expression, and growth rate, not recombinant protein production or metabolite co-production. Searches for those products and their coupling to microbial growth found no passage addressing the claim; page numbers were not provided in our copy. (LLM, conf=0.74)
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In the paper
“Based on previous studies, we can estimate that within 100 to 500 generations (corresponding to up to 2 months of selection for a typical E. coli or S. cerevisiae culture), a fitness increase of up to 50–100% can be achieved.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Moreover, it is important to note that the fitness increase as a function of the total number of generations is not linear (Figure 1c).”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“In recent ALE experiments various types of mutations were detected: Single-nucleotide polymorphisms (SNPs), small scale insertions and deletions (indels), transposable element (insertion sequence, IS) movements and amplifications as well as deletions of larger genomic regions (Figure 1d).”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
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In the paper
“During direct competition of an ancestral microbial strain and an adapted strain, the increased fitness of the adapted variant will be obvious by its increased frequency in the total population.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Thus, it cannot be assumed that a homogenous population is present during any point of a laboratory evolution experiment.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Stable phenotypes will accumulate rapidly, although clonal interference [42], bet hedging [43,60], genetic hitchhiking [61] and fluctuating growth environments can lead to significant population heterogeneity [22,62,63].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Recently, classical genetic engineering was successfully complemented with artificial laboratory selection of microbial cells in order to generate potentially robust and optimized microbial production systems [15,16].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Abstract
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In the paper
“Many typical ALE experiments were performed in shake flasks and similar growth conditions with cell densities in the range of 107 to 109 cells per mL for typical microbial cultures [124,125]”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“For standard ALE in biotechnology this is a critical factor, as prolonged selection that exceeds the first rapid evolutionary adaptation phase will not necessarily lead to significantly improved phenotypes [67];”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [67] source
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In the paper
“As such, ALE studies highlight that duplications and large scale genomic variations, although they can lead to significant issues such as genomic instability [152], play a major role in e.g. yeast evolution; this is also indicated by data on wine yeasts, galactose utilization, comparative genomics and drug resistance [115,153-156].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
What the sources say
- Not checked yetcites [152] source
- Could not verifycites [115] sourceExperimental — accuracy not yet measured
Citation [152] is attached to the claim that duplications and large-scale genomic variations can cause genomic instability. The paper discusses deleterious gene-dosage changes and the loss of duplicated copies through recombination (section “The Magnitude of the Problem,” page unavailable), but the passages found do not say that these changes cause genomic instability. The yeast-evolution claim is attached to other citations. (LLM, conf=0.72)
- Not checked yetcites [153] source
- Could not verifycites [154] sourceExperimental — accuracy not yet measured
Citation [152] is attached to the qualification about genomic instability, not the later statement about yeast evolution. The Introduction and Discussion discuss the evolution of ER-stress responses in Candida glabrata, but our copy does not address whether duplications or large-scale genomic variations cause genomic instability. Searches for genomic instability, duplication, and copy-number variation found no relevant passage. (LLM, conf=0.75)
- Could not verifycites [155] sourceExperimental — accuracy not yet measured
The Background and Results and Discussion discuss salt-responsive gene expression and adaptation in Hortaea werneckii, not duplications or large-scale genomic variation as drivers of yeast evolution. Searches for duplicated genes, genomic instability, and evolution found no passage addressing that claim in our copy; the genomic-instability clause also has a separate citation in the citing sentence. (LLM, conf=0.75)
- Could not verifycites [156] sourceExperimental — accuracy not yet measured
Citation [152] is attached to the claim that duplications and large-scale genomic variations can cause genomic instability. The Background discusses T-DNA insertions in Arabidopsis, and the Discussion concerns metabolite-data normalization; neither addresses that claim. Searches for duplications, genomic instability, and yeast evolution found no relevant passage in our copy. (LLM, conf=0.76)
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In the paper
“In summary Tables 1 and Table 2, it can be seen that a typical ALE experiment is performed for somewhat between 100 and 2000 generations and usually takes a few weeks up to a few months.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Moreover, biological catalysis offers several advantages over chemical synthesis, such as stereo-selective production of chemical compounds [9].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Abstract
What the sources say
- Not checked yetcites [9] source
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In the paper
“Synthetic biology is a new emerging field [10,11] and systems metabolic engineering has proven very successful for the design and implementation of biotechnological production processes [12-14].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Abstract
What the sources say
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In the paper
“As indicated in Figure 1a, in serial batch cultures for ALE, the transfer often occurs before the stationary phase is reached. Clearly, this is a prerequisite to avoid stationary phase adaptation [52].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Laboratory selection methods
What the sources say
- Not checked yetcites [52] source
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In the paper
“Microbial cells offer important advantages for ALE studies: (a) most microbial cells have simple nutrient requirements, (b) they can be easily cultivated in the laboratory and (c) microbial cells generally grow very fast and can be cultivated for several hundred generations within several weeks or months”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution
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In the paper
“however, particularly in the last 25 years, there has been an ever increasing number of such experiments with Escherichia coli and Saccharomyces cerevisiae being the most prominent organisms under investigation [26-28].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution
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In the paper
“This single parallel E. coli adaptation experiment is already exceeding 50000 generations [33-35].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution
What the sources say
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In the paper
“In this context, we cannot clearly predict the scale at which improved phenotypes emerge during laboratory evolution, although recent literature indicates that such predictions are possible in certain growth contexts such as carbon source adaptation [65].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [65] source
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Whereas certain environments can lead to fast selection of improved phenotypes, others, including the long-term adaptation to environmental pH [59,63], represent complex environments where microbial cells show low adaptive potential in terms of absolute fitness gain.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
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In the paper
“Whereas the fitness increase is usually fast within the first 100 to 500 generations, it slows considerably down during the course of ALE [36].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [36] source
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In the paper
“In this context, cells selected under growth limiting conditions can show growth trade-offs in non-limiting conditions and vice versa[53].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Laboratory selection methods
What the sources say
- Not checked yetcites [53] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Hence, adaptive laboratory evolution was already performed about a hundred years ago by William Dallinger [22] and during the middle of the last century [24,25];”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution
What the sources say
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The initial choice of conditions, including media composition and limited versus non-limited growth rate, will greatly influence whether the artificially selected microbial host will be suitable for its dedicated application.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Laboratory selection methods
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In the paper
“During adaptive evolution, certain trait values change and are associated with increased (Darwinian) fitness [20]; as such, an improved phenotype or property is often equal to increased fitness.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [20] source
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In the paper
“In certain cases ALE can lead to an even higher increase of up to 1000% as recently shown for the iron reduction rate of Geobacter sulfurreducens[123], although this increase was only achieved after 24 months of selection”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [123] source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Deletions accounted for approximately 29% of the observed genomic changes, followed by insertions (7%) and IS movements (3%) [15].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [15] source
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In the paper
“Nevertheless, the role of HGT in natural evolution remains a controversial topic [133].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [133] source
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In the paper
“Interestingly, it was shown that high mutation rates and mutator strains can emerge naturally during laboratory evolution and contribute to the formation of genetic novelty [33,73,139-141].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
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In the paper
“As summarized in a recent review, SNPs (61%, with G:C to T:A mutations being disproportionally frequent) account for the majority of observed genetic changes [15].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [15] source
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In the paper
“This so-called toolbox model suggests that prokaryotic metabolic pathways emerge through horizontal gene transfer (HGT) and are rapidly acquired and lost based on nutrient availability [132].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [132] source
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In the paper
“they are a prerequisite for the development of novel molecular functions [129-131].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“During the first few thousand generations, glucose-evolved cultures developed larger cell size and a lower final cell density as compared with the ancestor [34].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [34] source
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In the paper
“Furthermore, it was shown that mutational robustness tends to increase with mutation rate and decline with population size [40].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [40] source
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In the paper
“In this study, the biomass yield increased up to 40% and acetate overflow was reduced, whereas the metabolic rate increased and the evolved cells showed a lowered or total loss of motility.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [69] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Microbial metabolic networks often provide appropriate functions at a minimal size [134] and furthermore, their complexity seems to be correlated with environmental factors [135].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“however, such mutational adaptations might be counterproductive for some applications of microbial cells in biotechnology.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Many ALE studies analyzed the impact and molecular adaptation towards both stresses (Table 1 and Table 2), leading to major findings regarding the emergence of specialists, generalists, the underlying mutations and the applicability of evolved cells for industrial microbiology.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, an experimental E. coli culture could evolve the ability to aerobically utilize citrate [37], or the ability to use the non-natural carbon source 1,2-propanediol [71]; also, a strain deficient in glutathione biosynthesis was able to develop compensatory mutations to restore this function [147].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a 1997 study, E. coli was evolved in chemostat cultures in order to select for improved growth on glycerol. The authors reported phenotypic changes in terms of colony morphology accompanied with increased growth rate and biomass yield and decreased acetate formation [50].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [50] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It is clear that a higher mutation rate can only be beneficial to a certain extent as it also results in a genetic load [142].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Mutations and robustness
What the sources say
- Not checked yetcites [142] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In nature as well as in biotechnological processes, microorganisms are challenged with changing environmental conditions, where they experience fluctuations in temperature, pH, oxygenation, atmospheric or hydrostatic pressure but also water and nutrient availability; thus, the selective pressures can be divided in two main categories: nutrient availability and environmental stress [17].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses
What the sources say
- Not checked yetcites [17] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Only recently, the cumulative number of cell divisions (CCD) was proposed as a more appropriate denominator to evaluate microbial evolution [126].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptive laboratory evolution > Increased growth and fitness as desirable criteria
What the sources say
- Not checked yetcites [126] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Glucose import, sensing and regulation represent major targets during glucose-limited chemostat growth, as a further study also identified frequent mutations in HXT genes and glucose sensors and regulators such as RGT1 and MIG2[53].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [53] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Adaptive changes towards ethanol tolerance were linked to the up-regulation of oxyR and nrdR, indicating major changes in the cellular respiratory system but also changes in amino acid metabolism [85].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
What the sources say
- Not checked yetcites [85] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Transcript analysis showed up-regulation of trehalose and glycogen metabolism, whereas no mutations were identified in galactose or storage carbohydrate related genes. Interestingly, the authors rather identified mutations in RAS/PKA signaling as a source for increased fitness on galactose medium [106].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [106] source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The authors did not identify expression changes in HXT genes, although other studies on improved xylose and arabinose utilization indicated that HXT genes may also be involved in increased xylose uptake rates [99,104].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, Zelle and co-workers established growth on glucose by genetic- and evolutionary engineering in a pyruvate carboxylase-negative S. cerevisiae strain. The authors identified a point mutation in the recombinant sfcA gene, which shifted the co-factor preference from NADH to NADPH [107].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [107] source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mutations that lead to altered expression patterns accumulated predominantly in lacI and lacO1 regions of the lac operon [76]. Altogether, these mutations were responsible for a reduced (diauxic) lag phase and increased maximum growth rates in lactose growth medium.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [76] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“another study reported the emergence of aneuploidy during glucose-limited growth and amplification of the HXT6 gene with significant divergence between co-evolved populations [94].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [94] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Growth rates and glucose uptake rates increased up to 3.6 and up to 2.6 fold in evolved ∆pgi strains as compared with the ancestor and were accompanied with different phenotypes regarding acetate and formate production.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [70] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Early studies in glucose-limited chemostats revealed that glucose-limited selection led to increased biomass yield and a decreased fermentative capacity [93,98].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Decreased activity levels of enzymes related to glycolysis but also correlating changes in the expression levels of genes such as ENO1, ENO2, TDH1 and PYK1 and down-regulation of the stress response (MSN2/4) were observed.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [98] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Strikingly, the authors also noticed that malT regulatory mutations, although common in aerobic conditions, were absent during oxygen-limited chemostat growth, where mutations in the glucose permease ptsG were common [48].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [48] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“but most importantly the rpoS mutation alone did not positively influence the growth rate in the ancestral ∆pgi strain; rpoS mutations were epistatically linked to additional mutations.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [63] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Altered cell morphology was also observed, as well as higher affinity towards glucose, although no expression change in the major HXT low-affinity glucose transporters was observed [98]”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [98] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutations in acrAB and marC were found independently in these studies; further changes were linked to carbon and nitrogen metabolism via gatY and tnaA[86], enterobactin synthesis [63] or attenuated rpoS activity via hfq mutations [87].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In xylose adaptation studies, increased growth rates and higher ethanol yields were observed in recombinant yeast. In this case, trehalose and glycogen metabolic processes were significantly down-regulated, nutrient and stress signaling was affected by down-regulation of YAK1 and also accompanied by down-regulation of CWP1 and consequently major cell wall changes [108].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [108] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The authors found frequent point mutations in rpoS, udhA (soluble transhydrogenase), pntAB and a prophage deletion. They did not observe these mutations in the glucose-adapted wildtype strain; other regulatory mutations (including rpoABC) occurred in both backgrounds”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [70] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For other carbon sources, it was shown that selection for improved galactose utilization could be achieved by serial transfer with a 24% increase of μmax within 62 days. Galactose uptake rates and ethanol production were increased.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
What the sources say
- Not checked yetcites [106] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, experiments on pentose utilization highlighted that increased gene copy numbers of the heterologous genes in recombinant S. cerevisiae can emerge during evolutionary engineering and contribute to increased growth in anaerobic conditions [104,109].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Nutrient stress
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the model yeast S. cerevisiae, adaptation towards salt tolerance led to increased cell size and increased ploidy. Additionally, gene expression changes in CTT1 and MSN4 were observed, as well as a high-frequency SNP in the transcriptional regulator MOT2[116].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
What the sources say
- Not checked yetcites [116] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent study showed that cross-protection towards lignocellulosic hydrolysates can be evolved in S. cerevisiae. Interestingly, several mutants showed increased fitness in the presence of inhibitor combinations but reduced fitness when exposed to individual hydrolysate components [112].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
What the sources say
- Not checked yetcites [112] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, aerobic chemostat-selected S. cerevisiae cells also showed increased fitness in anaerobic glucose-limited chemostats and in acetate-limited chemostats, but decreased fitness in nitrogen-limited batch cultivations [53].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
What the sources say
- Not checked yetcites [53] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In fact, a recent study in S. cerevisiae indicated that anticipatory gene regulatory patterns can evolve under cycling salt and oxidative stress conditions on a laboratory time scale within 300 generations and that cross-stress protection against salt and oxidative stress is strikingly asymmetrical, with oxidative stress protecting against salt stress but not vice versa[120].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Non-conventional hosts – implications of ecological niches and genetic network architecture
What the sources say
- Not checked yetcites [120] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, evolutionary trade-offs and cross-protection against process-relevant parameters are ubiquitous, but the mode of cultivation and the specificities of the selection pressure largely determine to which extent these phenomena arise.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased copper tolerance was reported to be mediated by a genomic amplification of CUP1, decreased basal levels of the copper transporters CTR2 and CCC2 and decreased activity of antioxidant enzymes [117,128].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, epistatic interactions can be hardly inferred from metabolic modeling studies although significant epistatic connections for strain engineering may be easily identified in ALE studies.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“In another study, increased ethanol tolerance was mediated by mutations in the translational regulator SSD1 and UTH1, a protein of unknown function, and indicated that cell wall stability is a major factor in ethanol tolerance of S. cerevisiae[119].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
What the sources say
- Not checked yetcites [119] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From these data it can be concluded that: (a) long-term adaptation leads to both large-scale transcriptional de-regulation and optimization of terminal nodes (fine-tuning of the expression levels of individual genes)”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Environmental stress
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Glycerol-limited growth led to stable mutants in a single E. coli population, where one mutant showed increased growth in glycerol-sufficient batch cultures and a second mutant did not. Furthermore, the mutant that showed increased growth in batch culture also showed increased fitness under general nutrient limitation, heat and osmotic stress [50].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
What the sources say
- Not checked yetcites [50] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another interesting study analyzed to which extent multi-stress resistant S. cerevisiae populations can be evolved. The authors tested various chemostat and batch stress regimes and found that batch selection for freeze-thaw tolerance also selected for increased thermal, oxidative and ethanol stress resistance [113].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
What the sources say
- Not checked yetcites [113] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Yeast cells that were evolved for efficient galactose utilization [106] subsequently showed trade-offs when grown on glucose as carbon source. This effect was due to antagonistic pleiotropy that was based on mutations of the regulatory protein RAS2[162].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Whereas core sub-networks and pathways tend to be well conserved, the up- and downstream connections to other cellular networks vary significantly among different species and lead to species-specific differences of stress resistance in adverse environments [169,170]”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Non-conventional hosts – implications of ecological niches and genetic network architecture
What the sources say
- Not checked yetcites [169]
- Not checked yetcites [170]
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Examples for adaptive cross-protection are also available for S. cerevisiae where cobalt resistance also improved tolerance for other metal ions and pulsed cobalt stress exposure during laboratory evolution even resulted in evolutionary cross-protection to thermal and oxidative stress [114].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
What the sources say
- Not checked yetcites [114] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“and n-butanol tolerance is weakly compatible with oxidative stress [63] and leads to trade-offs in hexane and chloramphenicol resistance [86].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Adaptation towards nutrient sources and environmental stresses > Evolutionary trade-offs and cross-protection
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, for eukaryotic host organisms such as yeasts, alternating asexual and sexual propagation during selection can be applied in order to decouple beneficial and unsound mutations and thus reduce potential deficits of laboratory evolution experiments [118].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [118] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this context, computational approaches provide important benefits towards rational engineering of microbial cell factories but as it can be foreseen right now, they cannot replace or prevent ‘trial and error’ laboratory experiments for the foreseeable future.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
- Rests on an assumption: Enormous computational power is necessary to simulate living cells, even on a non-evolutionary scale.
- Rests on an assumption: Even for well-studied organisms such as E. coli and S. cerevisiae, approximately 30% of genes have unknown function.
- Rests on an assumption: The complex interactions of living organisms with their environment are not well understood.
- Rests on an assumption: Our understanding of the effect of many environmental stressors on cells, their precise action on certain cellular components, the mode of stress sensing, cellular signal transduction and cross-talk between signal transduction pathways is still limited.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast to classical approaches it is highly structured and biological networks are split into smaller functional modules [11,183], leading to complex optimization needs.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [11] source
- Not checked yetcites [183]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Full-scale models of microorganisms are available [185,186] and we can simulate microbial growth.”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [185]
- Not checked yetcites [186]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Towards this end, a recent study with S. cerevisiae and Saccharomyces paradoxus showed that the evolutionary rescue (ER) frequency was positively correlated with stress concentration during 100 generations of evolution in S. cerevisiae but negatively correlated in S. paradoxus[44].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Non-conventional hosts – implications of ecological niches and genetic network architecture
What the sources say
- Not checked yetcites [44] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other studies used ethylmethanesulfonate (EMS) treated Bacillus boroniphilus to select for increased boron resistance [88] or EMS-treated S. cerevisiae in order to achieve increased nutrient utilization and stress resistance [95,113,114].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, in silico approaches are widely applied in order to address evolutionary questions [40,172].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [40] source
- Not checked yetcites [172]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Microbial gene regulatory networks are generally very robust towards perturbations and large-scale re-wiring results in a significant number of viable clones with increased evolvability as compared with the wildtype [181].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [181]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Computational models are well-suited to study evolutionary change on the population level, whereas in silico evolution of artificial cells that include simulated regulatory networks are currently very limited [21].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [21] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Certain functions such as overflow metabolism in S. cerevisiae may have evolved in order to provide an evolutionary advantage in specific environments and to protect carbon resources from other competing species [175].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Non-conventional hosts – implications of ecological niches and genetic network architecture
What the sources say
- Not checked yetcites [175]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, laboratory selection can lead to large-scale rewiring of gene regulatory networks, but an approach, that the authors called gTME, global transcription machinery engineering, can also yield similar results [2].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [2] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Besides insights into co-evolutionary behavior, this approach can be exploited in order to increase antibiotic production such as in the case of co-cultivation of Streptomyces clavuligerus and Staphylococcus aureus[55].”
§ Adaptive laboratory evolution – principles and applications for biotechnology > Future directions
What the sources say
- Not checked yetcites [55] source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Mutations are the basis underlying genetic change and the selection of improved phenotypes in nature as well as in the laboratory.
“Mutations are the basis underlying genetic change and the selection of improved phenotypes in nature as well as in the laboratory.”
The paper relies on this without support.
Microbial cells evolved mechanisms to successfully cope with stressful conditions in order to maintain cellular homeostasis.
“Microbial cells evolved mechanisms to successfully cope with such stressful conditions in order to maintain cellular homeostasis.”
The paper relies on this without support.
Efficiency of nutrient source utilization is an important aspect of microbial growth and for industrial purposes.
“Efficiency of nutrient source utilization is an important aspect of microbial growth and for industrial purposes it may be governed by factors such as substrate cost or increased bioconversion rates.”
The paper relies on this without support.
In industrial processes microbial cells may be challenged with non-natural stresses that may result in poor and non-competitive process performance.
“In contrast to natural environments, in industrial processes microbial cells may be challenged with non-natural stresses that may result in poor and non-competitive process performance.”
The paper relies on this without support.
The total number of generations is commonly used to estimate the emergence of adaptive mutations.
“the total number of generations is commonly used to estimate the emergence of adaptive mutations.”
The paper relies on this without support.
The evolution of novel functions and pathways can be hardly observed in a laboratory evolution experiment, even with microbial cells and their fast growth rates.
“The evolution of novel functions and pathways can be hardly observed in a laboratory evolution experiment, even with microbial cells and their fast growth rates.”
The paper relies on this without support.
rpoS plays a crucial role towards survival in high osmotic conditions.
“Furthermore, it is known that rpoS plays a crucial role towards survival in high osmotic conditions.”
The paper relies on this without support.
Mesophilic organisms such as E. coli and S. cerevisiae have inherent properties that limit their use in certain applications, e.g. high temperature processes.
“Mesophilic organisms such as E. coli and S. cerevisiae have inherent properties that limit their use in certain applications, e.g. high temperature processes.”
The paper relies on this without support.
Limited data on the physiology of non-conventional organisms still represent a significant obstacle towards rational host cell engineering.
“Currently, limited data on the physiology of such organisms still represent a significant obstacle towards rational host cell engineering.”
The paper relies on this without support.
Enormous computational power is necessary to simulate living cells, even on a non-evolutionary scale.
“Enormous computational power is necessary to simulate living cells, even on a non-evolutionary scale.”
The paper relies on this without support.
Even for well-studied organisms such as E. coli and S. cerevisiae, approximately 30% of genes have unknown function.
“Additionally, even for well-studied organisms such as E. coli and S. cerevisiae, there is still a significant number (approximately 30%) of genes with unknown function.”
The paper relies on this without support.
The complex interactions of living organisms with their environment are not well understood.
“Furthermore, the complex interactions of living organisms with their environment are not well understood.”
The paper relies on this without support.
Our understanding of the effect of many environmental stressors on cells, their precise action on certain cellular components, the mode of stress sensing, cellular signal transduction and cross-talk between signal transduction pathways is still limited.
“Specifically, our understanding of the effect of many environmental stressors on cells, their precise action on certain cellular components, the mode of stress sensing, cellular signal transduction and cross-talk between signal transduction pathways is still limited.”
The authors state this as an assumption.
Evolution is constrained to work on available blueprints.
“As François Jacob pointed out: “Evolution is a tinkerer”, and as such evolution is constrained to work on available blueprints.”
The paper relies on this without support.
Genetic engineers have the possibility to rapidly construct novel circuits.
“However, genetic engineers have the possibility to rapidly construct novel circuits.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Adaptive evolutionary engineering based on metabolic engineering can allow microorganisms to quickly obtain excellent phenotypes, but there are problems such as unclear gene targets and negative mutation interference [90,91].”
From Recent Developments in Lignocellulosic Biofuels, a Renewable Source of Bioenergy (2022) · cites this paper as [90]
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Metadata
- Authors
- Dragosits, M., & Mattanovich, D.
- Affiliations
- BOKU University (AT)
- Corresponding author
- Dragosits, Martin
- Venue
- Microbial Cell Factories
- Published
- 2013
- Volume
- 12
- Issue
- 1
- Pages
- 64
- ISSN
- 1475-2859 (ISSN-L)
- PMC
- PMC3716822
- OpenAlex
- W2115941371
- Semantic Scholar
- 09e8fffffe29d6b53bee072e4f632e32239a43f8
- Cited by
- 827
- References
- 188
- Citations by year
- 2026: 80 · 2025: 85 · 2024: 99 · 2023: 69 · 2022: 63 · 2021: 80 · 2020: 84 · 2019: 67 · 2018: 66 · 2017: 52 · 2016: 36 · 2015: 23 · 2014: 21 · 2013: 2
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Microbial Cell Factories (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BOK:ePub (Universitätsbibliothek der Universität f Bodenkultur Wien) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- adaptive laboratory evolution, microbial engineering, molecular evolution, nutrient metabolism, stress metabolism, comparative genomics, transcriptomics, next-generation sequencing
- MeSH terms
- Biotechnology, Evolution, Molecular, Gene Regulatory Networks
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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