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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2014

Rewiring of genetic networks in response to modification of genetic background

Genome-scale genetic interaction networks are progressively contributing to map the molecular circuitry that determines cellular behaviour. To what extent this mapping changes in response to different environmental or genetic conditions is however largely unknown. Here we assembled a genetic network using an in silico model of metabolism in yeast to explicitly ask how separate genetic backgrounds alter network structure. Backgrounds defined by single deletions of metabolically active enzymes induce strong rewiring when the deletion corresponds to a catabolic gene, evidencing a broad redistribution of fluxes to alternative pathways. We also show how change is more pronounced in interactions linking genes in distinct functional modules, and in those connections that present weak epistasis. These patterns reflect overall the distributed robustness of catabolism. In a second class of genetic backgrounds, in which a number of neutral mutations accumulate, we dominantly observe modifications in the negative interactions that together with an increase in the number of essential genes indicate a global reduction in buffering. Notably, neutral trajectories that originate considerable changes in the wild-type network comprise mutations that diminished the environmental plasticity of the corresponding metabolism, what emphasizes a mechanistic integration of genetic and environmental buffering. More generally, our work demonstrates how the specific mechanistic causes of robustness influence the architecture of multiconditional genetic interaction maps.

Systems Biology↗

bioRxiv2016

The genetic Allee effect: a unified framework for the genetics and demography of small populations

The Allee effect is a theoretical model predicting low growth rates and the possible extinction of small populations. Historically, studies of the Allee effect have focused on demography. As a result, underlying processes other than the direct effect of population density on fitness components are not generally taken into account. There has been heated debate about the potential of genetic processes to drive small populations to extinction, but recent studies have shown that such processes clearly impact small populations over short time scales, and some may generate Allee effects. However, as opposed to the ecological Allee effect, which is underpinned by cooperative interactions between individuals, genetically driven Allee effects require a change in genetic structure to link the decline in population size with a decrease in fitness components. We therefore define the genetic Allee effect as a two-step process whereby a decrease in population size leads to a change in population genetic structure, and in turn, to a decrease in individual fitness. We describe potential underlying mechanisms, and review the evidence for this original type of component Allee effect, using published examples from both plants and animals. The possibility of considering demogenetic feedback in light of genetic Allee effects clarifies the analysis and interpretation of demographic and genetic processes, and the interplay between them, in small populations.

Ecology↗

bioRxiv2016

Quantifying the degree of sharing of genetic and non-genetic causes of gene expression variability across four tissues.

Gene expression can provide biological mechanisms which underlie genetic associations with complex traits and diseases, but often the most relevant tissue for the trait is inaccessible and a proxy is the only alternative. Here, we investigate shared and tissue specific patterns of variability in expression in multiple tissues, to quantify the degree of sharing of causes (genetic or non-genetic) of variability in gene expression among tissues. Using gene expression in ~800 female twins from the TwinsUK cohort in skin, fat, whole blood and lymphoblastoid cell lines (LCLs), we identified 9166 significant cis-eQTLs in fat, 9551 in LCLs, 8731 in skin and 5313 in blood (1% FDR). We observed up to 80% of cis-eQTLs are shared in pairs of tissues. In addition, the cis genetic correlation between tissues is > 90% for 35% of the genes, indicating for these genes a largely tissue-shared component of cis regulation. However, variance components show that cis genetic signals explain only a small fraction of the variation in expression, with from 67-87% of the variance explained by environmental factors, and 53% of the genetic effects occurring in trans. We observe a trans genetic correlation of 0 for all genes except a few which show correlation between fat and skin expression. The environmental effects are also observed to be entirely tissue specific, despite related tissues largely sharing exposures. These results demonstrate that patterns of gene expression are largely tissue specific, strongly supporting the need to study higher order regulatory interactions in the appropriate tissue context with large samples sizes and diversity of environmental contexts.

Genomics↗

bioRxiv2016

Diploid male production correlates with genetic diversity in the parasitoid wasp Venturia canescens: a genetic approach with new microsatellite markers

Sex determination is ruled by haplodiploidy in Hymenoptera, with haploid males arising from unfertilized eggs and diploid females from fertilized eggs. However, diploid males with null fitness are produced under Complementary Sex Determination (CSD), whenindividuals are homozygous for this locus. Diploid males are expected to be more frequent in genetically eroded populations (such as islands and captive populations), as genetic diversity at the csd locus should be low. However, only a few studies have focused on the relation between population size, genetic diversity and the proportion of diploid males in the field. Here, we developed new microsatellites markers in order to assess and compare genetic diversity and diploid male proportion in populations from three distinct habitat types (mainland, island or captive), in the parasitoid wasp Venturia canescens. Eroded genetic diversity and higher diploid male proportion were found in island and captive populations, and habitat type had large effect on genetic diversity. Therefore, diploid male proportion reflects the decreasing genetic diversity in small and isolated populations. Thus, Hymenopteran populations can be at high extinction risk due to habitat destruction or fragmentation.

Ecology↗

bioRxiv2022

Genetic variance and indirect genetic effects for affiliative social behavior in a wild primate

Affiliative social behaviors are linked to fitness components in multiple species. However, the role of genetic variance in shaping affiliative social behaviors remains largely unknown, limiting our understanding of how these behaviors can respond to natural selection. Here, we employed the animal model to estimate both environmental and genetic sources of variance and covariance in grooming behavior in the well-studied Amboseli baboon population in Kenya. We found that grooming given, grooming received, and total grooming all are similarly heritable (h2=0.22, h2=0.16, and h2=0.26 respectively), and that rank and the presence of kin contribute to environmental variance. We detected small but measurable indirect genetic effects of partner identity on the amount of grooming given within dyadic grooming partnerships. The genetic correlation between grooming given and grooming received was exceptionally strong and positive (R=0.94 {+/-} 0.12), and the indirect and direct genetic effects for grooming given were also strongly positively correlated (R=0.86 {+/-} 0.06). Our results provide insight into the evolvability of affiliative behavior in wild animals, including the possibility for correlations between direct and indirect genetic effects to accelerate the response to selection. As such they provide novel information about the genetic architecture of social behavior in nature, with important implications for the evolution of cooperation and reciprocity.

evolutionary biology↗

bioRxiv2025

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

genomics↗

bioRxiv2017

Insights to the genetic etiology of a lifestyle-related disease with differential levels of severity using a hierarchy of common genetic variants

Genome evolution in disparate species is synopsized to highlight the role of common genetic variants during their adaptation, and an evolutionary perspective is provided to infer lifestyle-related disease progression in humans. Cardiovascular disease (CVD) is a multi-factorial disease, where maladaptation due to a sedentary lifestyle and faulty diet can influence its prognosis, but the genetic basis for its differential severity remains unknown. As a healthy diet and lifestyle may restrict its prognosis, we hypothesize that a hierarchy of common genetic variants may differentially modulate that severity in a subpopulation. We suggest that the loss-of-function paradigm due to a genetic variant may give rise to a broad spectrum of CVD severity in conjunction with other variants. Here, we have inferred that CAD severity may be a consequence of the plasticity of common variants exclusive among patients with disparate disease severity. Most importantly, we have used a small and outbred subpopulation to demonstrate that common genetic variants can be exploited to trace this unique facet of CAD etiology. Moreover, we corroborate our hypothesis by reporting that a hierarchical plasticity of the LDLR gene, which has been implicated in a differential response to lipid metabolism, is associated with differential CVD severity.\n\nCan we gain insight to the genetic etiology of diseases using a limited number of genomes (few hundred)? Can small data sets lend insights that large data sets may subsequently confirm? Here, I show how common genetic variants, which were identified only from hundreds of individuals, may be used to gain unique insights regarding the disease etiology of a common lifestyle-related disease.

evolutionary biology↗

bioRxiv2019

Do genetic differences in growth thermal reaction norms maintain genetic variation in timing of diapause induction?

O_LIAn optimal timing for diapause induction through the sexual production of dormant propagules is expected in populations of annual organisms. Yet, experimental work typically finds high within-population genetic variation in the sexual production of such propagules. Thus, high genetic variation in timing for diapause induction should be a common feature of annual organisms. C_LIO_LIHere, we hypothesize that genetic variation in the propensity to produce diapause propagules, Pd, is maintained by a genotype-by-environment interaction in growth performance, where fast-growing genotypes within an environment should delay diapause relative to slow-growing genotypes. From this, we derive two predictions. First, if there is ecological crossover in growth performance, the genetic correlation of Pd between environments should be negative. Second, the correlation between absolute plasticities of growth and Pd should be negative. C_LIO_LIWe tested these predictions by quantifying ephippia production in genotypes of a population of the facultative sexual cladoceran Daphnia magna at two temperatures. The population biomass at the onset of ephippia production was used as a measure of Pd, whereas somatic growth rate was used to quantify growth. Plasticity for both measurements was derived from thermal reaction norms. C_LIO_LIOur results did not support either prediction, as neither the genetic correlation of Pd between environments, nor the correlation between absolute plasticity of growth and Pd were found to be significant. C_LIO_LIOur results suggest that genetic variation in the timing of diapause is not maintained by genetic differences in thermal growth reaction norms. We propose as an alternative hypothesis that if there is across year variation in how stochastically the environment deteriorates, fluctuating selection may favor genotypes with different Pd between years. C_LI

evolutionary biology↗

bioRxiv2017

High genetic loading for schizophrenia predicts poor response to lithium in patients with bipolar disorder: A polygenic score and cross-trait genetic analysis

ImportanceLithium is a first-line mood stabilizer for the maintenance treatment of Bipolar Disorder (BPD). However, the efficacy of lithium varies widely, with a non-response rate of up to 30%. Biological response markers and predictors are lacking.\n\nObjectiveGenetic factors are thought to mediate lithium treatment response, and the previously reported genetic overlap between BPD and schizophrenia (SCZ) led us to test whether a polygenic score (PGS) for SCZ could predict lithium treatment response in BPD. Further, we explored the potential molecular underpinnings of this association.\n\nDesignWeighted SCZ PGSs were computed at ten p-value thresholds (PT) using summary statistics from a genome-wide association study (GWAS) of 36,989 SCZ cases, and genotype data for BPD patients from the Consortium on Lithium Genetics (ConLi+Gen). For functional exploration, we performed a cross-trait meta-GWAS and pathway analysis, combining GWAS summary statistics on SCZ and lithium treatment response.\n\nSettingInternational multicenter GWAS.\n\nParticipantsPatients with BPD who had undergone lithium treatment were genotyped and retrospectively assessed for long-term treatment response (n=2,586).\n\nMain outcome measuresClinical treatment response to lithium was defined on both the categorical and continuous scales using the ALDA score. The effect measures include odds ratios (ORs) and the proportion of variance explained (R2), and a significant association was determined at p<0.05.\n\nResultsThe PGS for SCZ was inversely associated with lithium treatment response in the categorical outcome (p=8x10-5), at PT <5x10-2. Patients with BPD who had low polygenic load for SCZ responded better to lithium, with ORs for lithium response ranging from 3.46 [95%CI: 1.42-8.41 at 1st decile] to 2.03 [95%CI: 0.86-4.81 at the 9th decile], compared to the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA complex and inflammatory cytokines (TNF, IL-4, IFN{gamma}) as molecular contributors to lithium treatment response in BPD.\n\nConclusions and RelevanceThe study provides, for the first-time, evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.\n\nKey PointsO_ST_ABSQuestionC_ST_ABSDoes a polygenic score for Schizophrenia (SCZ) predict response to lithium in patients with Bipolar Disorder (BPD)? What are the molecular drivers of the association between SCZ and lithium treatment response?\n\nFindingsWe found an inverse association between genetic loading for SCZ risk variants and response to lithium in patients with BPD. Genetic variants in the HLA region on chromosome 6, the antigen presentation pathway and markers of inflammation (TNF, IL-4, IFN{gamma}) point to molecular underpinnings of lithium treatment response in BPD.\n\nMeaningIn patients with BPD, an assessment of a polygenic load for SCZ risk variants may assist in conjunction with clinical data to predict whether they would respond to lithium treatment.

genetics↗

bioRxiv2021

Landscape genetics across the Andes Mountains: Environmental variation drives genetic divergence in the leaf-cutting ant Atta cephalotes

Disentangling the mechanisms underlying spatial distribution of genetic variation into those due to environment or physical barriers from mere geographic distance is challenging in complex landscapes. The Andean uplift represents one of the most heterogeneous habitats where these questions remain unexplored as multiple mechanisms might interact, confounding their relative roles. We explore this broad question in the leaf-cutting ant Atta cephalotes, a species distributed across the Andes Mountains using nuclear microsatellite markers and mtCOI gene sequences. We investigate spatial genetic divergence across the Western range of Northern Andes in Colombia by testing the relative role of alternative scenarios of population divergence, including geographic distance (IBD), climatic conditions (IBE), and physical barriers due to the Andes Mountains (IBB). Our results reveal substantial genetic differentiation among A. cephalotes populations for both types of markers, but only nuclear divergence followed a hierarchical pattern with multiple models of genetic divergence imposed by the Western range. Model selection showed that IBD, IBE (temperature and precipitation), and IBB (Andes mountains) models, often proposed as individual drivers of genetic divergence, interact, and explain up to 33% of genetic divergence in A. cephalotes. IBE models remained significant after accounting for IBD, suggesting that environmental factors play a more prominent role when compared to IBB. These factors in combination with idiosyncratic dispersal patterns of ants appear to determine hierarchical patterns of gene flow. This study enriches our understanding of the forces shaping population divergence in complex habitat landscapes.

genetics↗

bioRxiv2019

Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval.

1Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. Taking advantage of recent clinical development advances and rapid growth in GWAS datasets, we extend the original work using updated data, test whether genetic evidence predicts future successes and introduce statistical models adjusting for target and indication-level properties. Our work confirms drugs with genetically supported targets were more likely to be successful in Phases II and III. When causal genes are clear (Mendelian traits and GWAS associations linked to coding variants), we find the use of human genetic evidence increases approval from Phase I by greater than two-fold, and, for Mendelian associations, the positive association holds prospectively. Our findings suggest investments into genomics and genetics are likely to be beneficial to companies deploying this strategy.

genetics↗

bioRxiv2026

The contribution of non-additive genetic effects to the genetic variance of polyploid species.

Whole genome duplication is a common mutation in eukaryotes with far-reaching phenotypic effects. The resulting morphological, physiological, and fitness consequences and how they affect the survival probability of newly polyploid lineages are intensively studied, but very little is known about the effect of genome doubling on the short-term evolvability of populations. Understanding the effect of polyploidization on the adaptive potential of populations is of crucial importance to predict the future of polyploid populations. In this paper, I investigate the immediate consequences of genome doubling on the genetic variance of populations. To do so, I performed numerical iterations and simulations of how the genetic variance of a quantitative trait changes after polyploidization, under different genetic architectures (additivity, dominance, and epistasis). I found that genetic variance generally decreases after genome doubling. Non-additive gene actions can make autotetraploid populations genetically more diverse than their diploid progenitors in rare cases, notably with overdominance and directional epistasis. By collecting estimates from the agronomic literature, I found that both dominance and epistatic variance contribute to the genetic variance of polyploid populations. These results bring new insights into the adaptive potential of newly formed tetraploid populations, and call for further experimental investigations of how polyploidization is associated with a short-term decrease in evolvability.

genetics↗

bioRxiv2017

The human brain views selfish behaviour towards genetic vs. non-genetic sibling differently

Previous behavioural studies have shown that humans act more altruistically towards kin. Whether and how such kinship preference translates into differential neurocognitive evaluation of social interactions has remained an open question. Here, we investigated how the human brain is engaged when viewing a moral dilemma between genetic vs. non-genetic sisters. During functional magnetic resonance imaging, a movie depicting refusal of organ donation between two sisters was shown, with participants guided to believe the sisters were related either genetically or by adoption. The participants selfreported that genetic relationship was not relevant to them, yet their brain activity told a different story. When the participants believed that the sisters were genetically related, inter-subject similarity of brain activity was significantly stronger in areas supporting response-conflict resolution, emotion regulation, and self-referential social cognition. Our results show that mere knowledge of a genetic relationship between interacting persons can robustly modulate social cognition of the perceiver.

neuroscience↗

bioRxiv2020

Convergent genetic architecture underlies parallel pelvic reduction in genetically highly structured stickleback species

Repeated and independent adaptation to specific environmental conditions from standing genetic variation is common. However, if genetic variation is limited, the evolution of similar locally adapted traits may be restricted to genetically different and potentially less optimal solutions or prevented from happening altogether. Using a quantitative trait locus (QTL) mapping approach, we identified the genomic regions responsible for the repeated pelvic reduction (PR) in three crosses between nine-spined stickleback populations expressing full and reduced pelvic structures. In one cross, PR mapped to linkage group 7 (LG7) containing the gene Pitx1, known to control pelvic reduction also in the three-spined stickleback. In the two other crosses, PR was polygenic and attributed to ten novel QTL, of which 90% were unique to specific crosses. When screening the genomes from 27 different populations for deletions in the Pitx1 regulatory element, these were only found in the population in which PR mapped to LG7, even though the morphological data indicated large effect QTL for PR in several other populations as well. Consistent with the available theory and simulations parameterised on empirical data, we hypothesise that the observed variability in genetic architecture of PR is due to heterogeneity in the spatial distribution of standing genetic variation caused by >2x stronger population structuring among freshwater populations and >10x stronger genetic isolation by distance in the sea in nine-spined sticklebacks as compared to three-spined sticklebacks.

evolutionary biology↗

bioRxiv2022

Genetic Diversity, Population Structure and Parentage Analysis in Brazilian Grapevine Hybrids after Half a Century of Genetic Breeding

In the 1940s, the Agronomic Institute of Campinas (IAC) started a grapevine breeding program to develop new cultivars adapted to the tropical and subtropical regions of Brazil. More than 2,000 crosses were carried out over 50 years, using 850 varieties as parents. However, among the thousands of hybrids developed by the program, only 130 are still maintained in the IAC grapevine germplasm collection. Little is known about their genetic makeup and usefulness for current breeding programs. In this study, we genotyped 130 Brazilian grape hybrids at 21 polymorphic microsatellite markers to evaluate the genetic diversity and population structure of the hybrids and verified their disclosed pedigrees. The results showed that the hybrid collection is highly diverse, with an expected heterozygosity (HE) of 0.80 and an observed heterozygosity (Ho) of 0.78. Strong structure in three subgroups based mainly on the usage and combination of parental groups was revealed by STRUCTURE software and confirmed by discriminant analysis of principal components (DAPC). Through molecular profiling analysis, fourteen synonyms, one homonym and one duplicate were identified. Parentage analysis confirmed 24 full parentages, as well as 33 half-kinships. In addition, 18 pedigrees were invalidated, and seven mislabeling events were identified. No compatible parent was identified for 33% of the IAC hybrids, highlighting severe genetic erosion in the IAC germplasm. The molecular characterization of the breeding hybrid bank collection contributes to our understanding of the genetic basis of the varieties, guiding the efficient utilization of available genetic diversity. Together, our results could be applied to other breeding programs and assist in the selection of parents, management of the breeding collection, and conservation of grapevine genetic resources.

molecular biology↗

bioRxiv2022

Approximate Bayesian Computation applied to time series of population genetic data disentangles rapid genetic changes and demographic variations in a pathogen population

Adaptation can occur at remarkably short timescales in natural populations, leading to drastic changes in phenotypes and genotype frequencies over a few generations only. The inference of demographic parameters can allow understanding how evolutionary forces interact and shape the genetic trajectories of populations during rapid adaptation. Here we propose a new Approximate Bayesian Computation (ABC) framework that couples a forward and individual-based model with temporal genetic data to disentangle genetic changes and demographic variations in a case of rapid adaptation. We test the accuracy of our inferential framework and evaluate the benefit of considering the full trajectory compared to few time samples. Theoretical investigations demonstrate high accuracy in both model and parameter estimations, even if a strong thinning is applied to time series data. Then, we apply our ABC inferential framework to empirical data describing the population genetics changes of the poplar rust pathogen following a major event of resistance overcoming. We successfully estimate key demographic and genetic parameters, including the proportion of resistant hosts deployed in the landscape and the level of standing genetic variation from which selection occurred. Inferred values are in accordance with our empirical knowledge of this biological system. This new inferential framework, which contrasts with coalescent-based ABC analyses, is promising for a better understanding of evolutionary trajectories of populations subjected to rapid adaptation.

evolutionary biology↗

bioRxiv2023

RATTACA: Genetic predictions in Heterogeneous Stock rats offer a new tool for genetic correlation and experimental design

Genetic correlations between traits are a common first step in studies identifying causal genetic pathways and mechanisms. Using this framework with inbred or selected lines, however, requires intensive labor investment through breeding and phenotyping, and is prone to confounding, as observed trait correlations do not necessarily reflect a causative genetic architecture shared between distinct populations. When drawn from a single outbred population, genetic trait predictions offer a viable alternative to experimental phenotyping and can be used to identify putative genetic correlations when samples with divergent trait predictions also diverge in a second measured trait. Here, we present a novel research paradigm and service called RATTACA, in which genotypes from Heterogenous Stock (HS) rats are used to predict trait values using linear mixed models. These predictions are used to select samples of individuals with high and low extreme trait values, facilitating (1) a priori sampling of desired trait values without oversampling across phenotypic space and (2) easy identification of putative genetic correlations between predicted and newly measured traits. We validated prediction models using four example phenotypes with measured trait values and found sufficient accuracy to distinguish extreme trait samples, even when using a small number of genome-wide variants (n = 50,000) for traits with modest heritability (h2 = 0.13). Given genotypes and trait measurements available through previous research in HS rats, we propose RATTACA as a service to reliably predict more than 80 behavioral and physiological traits.

genomics↗

bioRxiv2023

Genomically integrated orthogonal translation in Escherichia coli, a new synthetic auxotrophic chassis with altered genetic code, genetic firewall, and enhanced protein expression

In the last three decades, genetic code engineering has expanded protein biosynthesis options from the natural set of 20 canonical amino acids to over 250 non-canonical amino acids (ncAAs). This progress involves rewiring of protein translation by establishing Orthogonal Translation Systems (OTS) through orthogonal pairs. Traditionally encoded on plasmid vectors, these systems are often unstable and burdensome in large-scale fermentations. To moving forward from academia to reliable technology, it is crucial to integrate OTS genetic modules stably into a molecular chassis with a defined genome background. Here, we demonstrate genomically integrated OTS in Escherichia coli, creating a synthetic auxotrophic chassis with an altered genetic code. Using CRISPR-associated transposase tool (CASTs), we targeted multiple genome sites, inserting OTS components (enzymes, tRNA genes) non-disruptively. Our OTS system demonstrated site-specific incorporation of m-oNB-Dopa through in-frame amber stop codon readthrough, enabling the expression of smart underwater bioglues. Simple metabolic labelling, introducing fluoroproline analogs enhancing conformational stability during orthogonal translation, further bolstered system robustness. These chassis, equipped also with synthetic auxotrophy for m-oNB-Dopa, serve as a built-in genetic barrier (genetic firewall), ensuring safe bioproduction in genetically isolated settings. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/567690v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@a7a3e0org.highwire.dtl.DTLVardef@1f7d3c5org.highwire.dtl.DTLVardef@1703dfcorg.highwire.dtl.DTLVardef@1f584bf_HPS_FORMAT_FIGEXP M_FIG C_FIG One-sentence AbstractCRISPR-assisted transposition has enabled the development of a robust and biosafe Escherichia coli-based chassis with genomically integrated orthogonal translation components, enhancing synthetic protein production and laying the foundation for the transition of this research field from academia to reliable technology.

synthetic biology↗