The GENETIC BASIS OF HYPER-SYNTHESIS OF SS-Galactosidase

Horiuchi, Tadao; Horiuchi, Sumiko; Novick, Aaron

doi:10.1093/genetics/48.2.157

Cited by 97 publications

(8 citation statements)

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“…It has been extensively described as a means to confer or increase resistance to environmental stresses such as antibiotics (20) or heavy metals (32). The gene amplification could also be involved in adaptation to environments with limited nutrient concentration, usually by increasing limiting substrate uptake or processing (33)(34)(35). Here, we report the amplification of central carbon metabolism actors in response to a redox imbalance.…”

Section: Discussionmentioning

confidence: 81%

Genetic Plasticity and Ethylmalonyl Coenzyme A Pathway during Acetate Assimilation in Rhodospirillum rubrum S1H under Photoheterotrophic Conditions

Meur

Deutschbauer

Koch

et al. 2018

Appl Environ Microbiol

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Purple nonsulfur bacteria represent a promising resource for biotechnology because of their great metabolic versatility. has been widely studied regarding its metabolism of volatile fatty acid, mainly acetate. As the glyoxylate shunt is unavailable in, the citramalate cycle pathway and the ethylmalonyl-coenzyme A (CoA) pathway are proposed as alternative anaplerotic pathways for acetate assimilation. However, despite years of debate, neither has been confirmed to be essential. Here, using functional genomics, we demonstrate that the ethylmalonyl-CoA pathway is required for acetate photoassimilation. Moreover, an unexpected reversible long-term adaptation is observed, leading to a drastic decrease in the lag phase characterizing the growth of in the presence of acetate. Using proteomic and genomic analyses, we present evidence that the adaptation phenomenon is associated with reversible amplification and overexpression of a 60-kb genome fragment containing key enzymes of the ethylmalonyl-CoA pathway. Our observations suggest that a genome duplication and amplification phenomenon is not only involved in adaptation to acute stress but can also be important for basic carbon metabolism and the redox balance. Purple nonsulfur bacteria represent a major group of anoxygenic photosynthetic bacteria that emerged as a promising resource for biotechnology because of their great metabolic versatility and ability to grow under various conditions. S1H has notably been selected by the European Space Agency to colonize its life support system, called MELiSSA, due to its capacity to perform photoheterotrophic assimilation of volatile fatty acids (VFAs), mainly acetate. VFAs are valuable carbon sources for many applications, combining bioremediation of contaminated environments with the generation of added-value products. Acetate is one of the major volatile fatty acids generated as a by-product of fermentation processes. In, purple nonsulfur bacteria, the assimilation of acetate is still under debate since two different pathways have been proposed. Here, we clearly demonstrate that the ethylmalonyl-CoA pathway is the major anaplerotic pathway for acetate assimilation in this strain. Interestingly, we further observed that gene duplication and amplification, which represent a well-known phenomenon in antibiotic resistance, also play a regulatory function in carbon metabolism and redox homeostasis.

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Section: Discussionmentioning

confidence: 81%

Genetic Plasticity and Ethylmalonyl Coenzyme A Pathway during Acetate Assimilation in Rhodospirillum rubrum S1H under Photoheterotrophic Conditions

Meur

Deutschbauer

Koch

et al. 2018

Appl Environ Microbiol

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“…Although the notion of duplication producing redundant genes is central to current theories of duplicated gene evolution, the short-term benefits of gene duplications are well known. This is illustrated by the numerous observations of adaptive gene amplifications in response to antibiotics [ 31 , 32 , 33 ], anticancer drug treatments and exposure to various toxins [ 34 , 35 , 36 , 37 , 38 , 39 ] or heavy metals [ 40 , 41 , 42 , 43 , 44 ], nutrient limitations [ 32 , 33 , 45 , 46 , 47 , 48 , 49 , 50 ], pesticide treatments [ 51 , 52 , 53 ], extreme temperatures [ 54 , 55 ] and symbiotic and parasitic interactions [ 56 , 57 ]. Combining this information with the observations that recently duplicated genes evolve under purifying selection ([ 21 ] and our present work), it seems reasonable to hypothesize that a majority of duplicated genes that achieve fixation in a population increase fitness when present in two or more copies in a genome and thus are subject to purifying selection from the moment of duplication.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the observation that purifying selection appears to act on all recent duplicates and examination of the functions of recently duplicated genes do not support the notion that gene duplication results in true functional redundancy and duplications may achieve fixation despite being redundant [ 26 ]. The alternative hypothesis - that gene duplications are fixed in a population by positive selection in all organisms - is supported by a combination of evidence of adaptive duplications from many types of living organisms: prokaryotes [ 31 , 33 , 45 , 46 , 48 , 50 , 55 , 56 ], protists [ 35 , 58 , 59 ], plants [ 39 , 44 ], fungi [ 43 , 49 ], invertebrates [ 40 , 41 , 51 , 52 , 53 ], non-mammalian vertebrates [ 54 ], as well as mammalian somatic tissues [ 34 , 36 , 37 , 38 ]. Combining these observations with the suggestion that gene duplication may be a general mechanism of adaptation to various conditions of environmental stress [ 32 , 33 , 46 , 48 , 49 , 50 , 52 , 53 , 55 , 60 ], we suggest that, in both prokaryotes and eukaryotes, most paralogs that are fixed in a population have a direct effect on fitness from the moment of duplication, and aid in the adaptation to various environmental conditions, primarily through a protein dosage effect.…”

Section: Discussionmentioning

confidence: 99%

Selection in the evolution of gene duplications

et al. 2002

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BackgroundGene duplications have a major role in the evolution of new biological functions. Theoretical studies often assume that a duplication per se is selectively neutral and that, following a duplication, one of the gene copies is freed from purifying (stabilizing) selection, which creates the potential for evolution of a new function.ResultsIn search of systematic evidence of accelerated evolution after duplication, we used data from 26 bacterial, six archaeal, and seven eukaryotic genomes to compare the mode and strength of selection acting on recently duplicated genes (paralogs) and on similarly diverged, unduplicated orthologous genes in different species. We find that the ratio of nonsynonymous to synonymous substitutions (Kn/Ks) in most paralogous pairs is <<1 and that paralogs typically evolve at similar rates, without significant asymmetry, indicating that both paralogs produced by a duplication are subject to purifying selection. This selection is, however, substantially weaker than the purifying selection affecting unduplicated orthologs that have diverged to the same extent as the analyzed paralogs. Most of the recently duplicated genes appear to be involved in various forms of environmental response; in particular, many of them encode membrane and secreted proteins.ConclusionsThe results of this analysis indicate that recently duplicated paralogs evolve faster than orthologs with the same level of divergence and similar functions, but apparently do not experience a phase of neutral evolution. We hypothesize that gene duplications that persist in an evolving lineage are beneficial from the time of their origin, due primarily to a protein dosage effect in response to variable environmental conditions; duplications are likely to give rise to new functions at a later phase of their evolution once a higher level of divergence is reached.

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“…Estimates of de novo CNV rates are derived from indirect and imprecise methods, and even when genome-wide mutation rates are directly quantified by mutation accumulation studies and whole-genome sequencing, estimates depend on both genotype and condition [2] and vary by orders of magnitude. Reported frequencies of duplications per locus per generation range from 10 -6 to 10 -2 in Escherichia coli and Salmonella [24][25][26][27][28][29], 10 -6 to 10 -4 in Drosophila [30,31], 10 -7 to 10 -5 in human sperm [32,33], and 10 -12 to 10 -6 in the yeast Saccharomyces cerevisiae [34][35][36][37][38]. Reported rates of large scale duplications and aneuploidy in S. cerevisiae are 10 -5 to 10 -4 per cell per division [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Simulation-based inference of evolutionary parameters from adaptation dynamics using neural networks

Avecilla

Gresham

Ram

2021

Preprint

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The rate of adaptive evolution depends on the rate at which beneficial mutations are introduced into a population and the fitness effects of those mutations. The rate of beneficial mutations and their expected fitness effects is often difficult to empirically quantify. As these two parameters determine the pace of evolutionary change in a population, the dynamics of adaptive evolution may enable inference of their values. Copy number variants (CNVs) are a pervasive source of heritable variation that can facilitate rapid adaptive evolution. Previously, we developed a locus-specific fluorescent CNV reporter to quantify CNV dynamics in evolving populations maintained in nutrient-limiting conditions using chemostats. Here, we use the observed CNV adaptation dynamics to estimate the rate at which beneficial CNVs are introduced through de novo mutation and their fitness effects using simulation-based Bayesian likelihood-free inference approaches. We tested the suitability of two evolutionary models: a standard Wright-Fisher model and a chemostat growth model. We evaluated two likelihood-free inference algorithms: the well-established Approximate Bayesian Computation with Sequential Monte Carlo (ABC-SMC) algorithm, and the recently developed Neural Posterior Estimation (NPE) algorithm, which applies an artificial neural network to directly estimate the posterior distribution. By systematically evaluating the suitability of different inference methods and models we show that NPE has several advantages over ABC-SMC and that a Wright-Fisher evolutionary model suffices in most cases. Using our validated inference framework, we estimate the CNV formation rate at the GAP1 locus in yeast as 10-4.7 -10-4 per cell division, and a selection coefficient of 0.04 - 0.1 per generation for GAP1 CNVs in glutamine-limited chemostats. We experimentally validated our estimates using barcode lineage tracking and pairwise fitness assays. Our results are consistent with a high beneficial CNV supply rate that is 10-fold greater than the estimated rates of beneficial single-nucleotide mutations, explaining their outsized importance in rapid adaptive evolution. More generally, our study demonstrates the utility of novel simulation-based likelihood-free inference methods for inferring the rates and effects of evolutionary processes from empirical data.

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The GENETIC BASIS OF HYPER-SYNTHESIS OF SS-Galactosidase

Cited by 97 publications

References 0 publications

Genetic Plasticity and Ethylmalonyl Coenzyme A Pathway during Acetate Assimilation in Rhodospirillum rubrum S1H under Photoheterotrophic Conditions

Genetic Plasticity and Ethylmalonyl Coenzyme A Pathway during Acetate Assimilation in Rhodospirillum rubrum S1H under Photoheterotrophic Conditions

Selection in the evolution of gene duplications

Simulation-based inference of evolutionary parameters from adaptation dynamics using neural networks

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