scholarly journals Drift barriers to quality control when genes are expressed at different levels

2016 ◽  
Author(s):  
K Xiong ◽  
JP McEntee ◽  
DJ Porfirio ◽  
J Masel
Keyword(s):  
Gene Expression ◽  
Population Size ◽  
Extreme Case ◽  
Error Rates ◽  
Gradual Transition ◽  
Effective Population ◽  
Buchnera Aphidicola ◽  
E Coli ◽  
C Elegans ◽  
Large Populations

ABSTRACTGene expression is imperfect, sometimes leading to toxic products. Solutions take two forms: globally reducing error rates, or ensuring that the consequences of erroneous expression are relatively harmless. The latter is optimal, but because it must evolve independently at so many loci, it is subject to a stringent “drift barrier” – a limit to how weak the effects of a deleterious mutation s can be, while still being effectively purged by selection, expressed in terms of the population size N of an idealized population such that purging requires s < −1/N. In previous work, only large populations evolved the optimal local solution, small populations instead evolved globally low error rates, and intermediate populations were bistable, with either solution possible. Here we take into consideration the fact that the effectiveness of purging varies among loci, because of variation in gene expression level and variation in the intrinsic vulnerabilities of different gene products to error. The previously found dichotomy between the two kinds of solution breaks down, replaced by a gradual transition as a function of population size. In the extreme case of a small enough population, selection fails to maintain even the global solution against deleterious mutations, explaining the non-monotonic relationship between effective population size and transcriptional error rate that was recently observed in experiments on E. coli, C. elegans and Buchnera aphidicola.

scholarly journals High Transcriptional Error Rates Vary as a Function of Gene Expression Level

2019 ◽  
Vol 12 (1) ◽  
pp. 3754-3761 ◽  
Author(s):  
Kendra M Meer ◽  
Paul G Nelson ◽  
Kun Xiong ◽  
Joanna Masel
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Sample Preparation ◽  
Error Rate ◽  
Error Rates ◽  
Effective Population ◽  
E Coli ◽  
Population Sizes ◽  
Local Robustness

Abstract Errors in gene transcription can be costly, and organisms have evolved to prevent their occurrence or mitigate their costs. The simplest interpretation of the drift barrier hypothesis suggests that species with larger population sizes would have lower transcriptional error rates. However, Escherichia coli seems to have a higher transcriptional error rate than species with lower effective population sizes, for example Saccharomyces cerevisiae. This could be explained if selection in E. coli were strong enough to maintain adaptations that mitigate the consequences of transcriptional errors through robustness, on a gene by gene basis, obviating the need for low transcriptional error rates and associated costs of global proofreading. Here, we note that if selection is powerful enough to evolve local robustness, selection should also be powerful enough to locally reduce error rates. We therefore predict that transcriptional error rates will be lower in highly abundant proteins on which selection is strongest. However, we only expect this result when error rates are high enough to significantly impact fitness. As expected, we find such a relationship between expression and transcriptional error rate for non-C→U errors in E. coli (especially G→A), but not in S. cerevisiae. We do not find this pattern for C→U changes in E. coli, presumably because most deamination events occurred during sample preparation, but do for C→U changes in S. cerevisiae, supporting the interpretation that C→U error rates estimated with an improved protocol, and which occur at rates comparable with E. coli non-C→U errors, are biological.

scholarly journals High transcriptional error rates vary as a function of gene expression level

2019 ◽  
Author(s):  
K.M. Meer ◽  
P.G. Nelson ◽  
K. Xiong ◽  
J. Masel
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Sample Preparation ◽  
Error Rate ◽  
Error Rates ◽  
Effective Population ◽  
E Coli ◽  
Population Sizes ◽  
Local Robustness

AbstractErrors in gene transcription can be costly, and organisms have evolved to prevent their occurrence or mitigate their costs. The simplest interpretation of the drift barrier hypothesis suggests that species with larger population sizes would have lower transcriptional error rates. However, Escherichia coli seems to have a higher transcriptional error rate than species with lower effective population sizes, e.g. Saccharomyces cerevisiae. This could be explained if selection in E. coli were strong enough to maintain adaptations that mitigate the consequences of transcriptional errors through robustness, on a gene by gene basis, obviating the need for low transcriptional error rates and associated costs of global proofreading. Here we note that if selection is powerful enough to evolve local robustness, selection should also be powerful enough to locally reduce error rates. We therefore predict that transcriptional error rates will be lower in highly abundant proteins on which selection is strongest. However, we only expect this result when error rates are high enough to significantly impact fitness. As expected, we find such a relationship between expression and transcriptional error rate for non C➔U errors in E. coli (especially G➔A), but not in S. cerevisiae. We do not find this pattern for C➔U changes in E. coli, presumably because most deamination events occurred during sample preparation, but do for C➔U changes in S. cerevisiae, supporting the interpretation that C➔U error rates estimated with an improved protocol, and which occur at rates comparable to E. coli non C➔U errors, are biological.

scholarly journals Effective Population Size Predicts Local Rates but Not Local Mitigation of Read-through Errors

2020 ◽  
Vol 38 (1) ◽  
pp. 244-262
Author(s):  
Alexander T Ho ◽  
Laurence D Hurst
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Stop Codon ◽  
Neutral Theory ◽  
Error Rates ◽  
Species Variation ◽  
Effective Population ◽  
Weak Selection ◽  
Error Mitigation ◽  
Good Proxy

Abstract In correctly predicting that selection efficiency is positively correlated with the effective population size (Ne), the nearly neutral theory provides a coherent understanding of between-species variation in numerous genomic parameters, including heritable error (germline mutation) rates. Does the same theory also explain variation in phenotypic error rates and in abundance of error mitigation mechanisms? Translational read-through provides a model to investigate both issues as it is common, mostly nonadaptive, and has good proxy for rate (TAA being the least leaky stop codon) and potential error mitigation via “fail-safe” 3′ additional stop codons (ASCs). Prior theory of translational read-through has suggested that when population sizes are high, weak selection for local mitigation can be effective thus predicting a positive correlation between ASC enrichment and Ne. Contra to prediction, we find that ASC enrichment is not correlated with Ne. ASC enrichment, although highly phylogenetically patchy, is, however, more common both in unicellular species and in genes expressed in unicellular modes in multicellular species. By contrast, Ne does positively correlate with TAA enrichment. These results imply that local phenotypic error rates, not local mitigation rates, are consistent with a drift barrier/nearly neutral model.

scholarly journals Repeatability of adaptation in experimental populations of different sizes

2015 ◽  
Vol 282 (1805) ◽  
pp. 20143033 ◽  
Author(s):  
Josianne Lachapelle ◽  
Joshua Reid ◽  
Nick Colegrave
Keyword(s):  
Population Size ◽  
Large Contribution ◽  
Unicellular Alga ◽  
Effective Population ◽  
Fitness Level ◽  
Relative Contribution ◽  
Large Populations ◽  
Population Sizes ◽  
Evolutionary Trajectories ◽  
Experimental Populations

The degree to which evolutionary trajectories and outcomes are repeatable across independent populations depends on the relative contribution of selection, chance and history. Population size has been shown theoretically and empirically to affect the amount of variation that arises among independent populations adapting to the same environment. Here, we measure the contribution of selection, chance and history in different-sized experimental populations of the unicellular alga Chlamydomonas reinhardtii adapting to a high salt environment to determine which component of evolution is affected by population size. We find that adaptation to salt is repeatable at the fitness level in medium ( N e = 5 × 10 4 ) and large ( N e = 4 × 10 5 ) populations because of the large contribution of selection. Adaptation is not repeatable in small ( N e = 5 × 10 3 ) populations because of large constraints from history. The threshold between stochastic and deterministic evolution in this case is therefore between effective population sizes of 10 3 and 10 4 . Our results indicate that diversity across populations is more likely to be maintained if they are small. Experimental outcomes in large populations are likely to be robust and can inform our predictions about outcomes in similar situations.

scholarly journals Spread of new mutations through space

2022 ◽  
Author(s):  
Kyle Shaw ◽  
Peter Beerli
Keyword(s):  
Population Density ◽  
Population Size ◽  
Simulation Software ◽  
Effective Population ◽  
Random Drift ◽  
Rate Of Spread ◽  
Large Populations ◽  
Discrete Population ◽  
Explicit Simulation ◽  
New Mutations

The terms population size and population density are often used interchangeably, when in fact they are quite different. When viewed in a spatial landscape, density is defined as the number of individuals within a square unit of distance, while population size is simply the total count of a population. In discrete population genetics models, the effective population size is known to influence the interaction between selection and random drift with selection playing a larger role in large populations while random drift has more influence in smaller populations. Using a spatially explicit simulation software we investigate how population density affects the flow of new mutations through a geographical space. Using population density, selectional advantage, and dispersal distributions, a model is developed to predict the speed at which the new allele will travel, obtaining more accurate results than current diffusion approximations provide. We note that the rate at which a neutral mutation spreads begins to decay over time while the rate of spread of an advantageous allele remains constant. We also show that new advantageous mutations spread faster in dense populations.

scholarly journals Population size influences the type of nucleotide variations in humans

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sankar Subramanian
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
High Frequency ◽  
Genetic Diseases ◽  
Large Population ◽  
Low Frequency ◽  
Small Population ◽  
Effective Population ◽  
Genome Data ◽  
Large Populations

Abstract Background It is well known that the effective size of a population (Ne) is one of the major determinants of the amount of genetic variation within the population. However, it is unclear whether the types of genetic variations are also dictated by the effective population size. To examine this, we obtained whole genome data from over 100 populations of the world and investigated the patterns of mutational changes. Results Our results revealed that for low frequency variants, the ratio of AT→GC to GC→AT variants (β) was similar across populations, suggesting the similarity of the pattern of mutation in various populations. However, for high frequency variants, β showed a positive correlation with the effective population size of the populations. This suggests a much higher proportion of high frequency AT→GC variants in large populations (e.g. Africans) compared to those with small population sizes (e.g. Asians). These results imply that the substitution patterns vary significantly between populations. These findings could be explained by the effect of GC-biased gene conversion (gBGC), which favors the fixation of G/C over A/T variants in populations. In large population, gBGC causes high β. However, in small populations, genetic drift reduces the effect of gBGC resulting in reduced β. This was further confirmed by a positive relationship between Ne and β for homozygous variants. Conclusions Our results highlight the huge variation in the types of homozygous and high frequency polymorphisms between world populations. We observed the same pattern for deleterious variants, implying that the homozygous polymorphisms associated with recessive genetic diseases will be more enriched with G or C in populations with large Ne (e.g. Africans) than in populations with small Ne (e.g. Europeans).

scholarly journals The effect of population size on effective population size: an empirical study in the red flour beetle Tribolium castaneum

1996 ◽  
Vol 68 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Leslie A. Pray ◽  
Charles J. Goodnight ◽  
Lori Stevens ◽  
James M. Schwartz ◽  
Guiyun Yan
Keyword(s):  
Population Size ◽  
Tribolium Castaneum ◽  
Evolutionary Biology ◽  
Negative Relationship ◽  
Red Flour Beetle ◽  
Published Data ◽  
Effective Population ◽  
Flour Beetle ◽  
Large Populations ◽  
Population Sizes

SummaryDespite the increasing number of studies on the magnitude of Ne/N ratios, much remains unknown about the effects of demographic and environmental variables on Ne/N. We determined Ne/N for seven population size treatments, ranging from N = 2 to N = 960, in the red flour beetle Tribolium castaneum. Ne/N decreased with increasing N, as evidenced by a significant negative relationship between log N and Ne/N. Our results are consistent with other published data on the relationship between Ne/N and N. Effective population sizes in large populations may be much smaller than previously recognized. These results have important implications for conservation and evolutionary biology.

scholarly journals A TWO-LOCUS NEUTRALITY TEST: APPLICATIONS TO HUMANS, E. COLI AND LODGEPOLE PINE

Genetics ◽  
1986 ◽  
Vol 112 (1) ◽  
pp. 135-156
Author(s):  
Philip W Hedrick ◽  
Glenys Thomson
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Lodgepole Pine ◽  
The Other ◽  
Effective Population ◽  
Recombination Rates ◽  
Neutrality Test ◽  
E Coli ◽  
Electrophoretic Data

ABSTRACT The expected disequilibrium between two loci with k alleles at one locus and l alleles at the other is given for a sample of size n drawn from a population under neutrality equilibrium. Three different measures of disequilibrium with 95% intervals are tabulated for combinations of n, k, l and 4Nc, where N is the effective population size and c is the amount of recombination between the loci. The extent and pattern of disequilibrium are strongly dependent upon 4Nc and are somewhat dependent on n, k and l. The 95% intervals are large, particularly for low numbers of alleles and low values of 4Nc. As examples, observed disequilibrium from histocompatibility loci in humans (HLA) and electrophoretic data in E. coli and lodgepole pine were compared to these theoretical values. Using information about recombination rates, the HLA data showed more disequilibrium than neutrality expectations, whereas electrophoretic data from E. coli and lodgepole pine had somewhat less disequilibrium than neutrality expectations.

scholarly journals Effects of FUdR on gene expression in the C. elegans bacterial diet OP50

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Grace McIntyre ◽  
Justin Wright ◽  
Hoi Tong Wong ◽  
Regina Lamendella ◽  
Jason Chan
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Expression Patterns ◽  
Growth Media ◽  
Bacterial Gene ◽  
Intestinal Microbes ◽  
E Coli ◽  
C Elegans ◽  
Bacterial Gene Expression ◽  
General Transport

Abstract Objective Many C. elegans aging studies use the compound 5-fluro-2ʹ-deoxyuridine (FUdR) to produce a synchronous population of worms. However, the effects of FUdR on the bacterial gene expression of OP50 E. coli, the primary laboratory C. elegans food source, is not fully understood. This is particularly relevant as studies suggest that intestinal microbes can affect C. elegans physiology. Therefore, it is imperative that we understand how exposure to FUdR can affect gene expression changes in OP50 E. coli. Results An RNAseq dataset comprised of expression patterns of 2900 E. coli genes in the strain OP50, which were seeded on either nematode growth media (NGM) plates or on FUdR (50 µM) supplemented NGM plates, was analyzed. Analysis showed differential gene expression in genes involved in general transport, amino acid biosynthesis, transcription, iron transport, and antibiotic resistance. We specifically highlight metabolic enzymes in the l-histidine biosynthesis pathway as differentially expressed between NGM and FUdR exposed OP50. We conclude that OP50 exposed to FUdR results in differential expression of many genes, including those in amino acid biosynthetic pathways.

scholarly journals Conserved rates and patterns of transcription errors across bacterial growth states and lifestyles

2016 ◽  
Vol 113 (12) ◽  
pp. 3311-3316 ◽  
Author(s):  
Charles C. Traverse ◽  
Howard Ochman
Keyword(s):  
Escherichia Coli ◽  
Cell Survival ◽  
Error Rates ◽  
Buchnera Aphidicola ◽  
Rna Sequences ◽  
E Coli ◽  
Genome Wide ◽  
Transcription Error ◽  
Bacterial Endosymbionts ◽  
Altered Proteins

Errors that occur during transcription have received much less attention than the mutations that occur in DNA because transcription errors are not heritable and usually result in a very limited number of altered proteins. However, transcription error rates are typically several orders of magnitude higher than the mutation rate. Also, individual transcripts can be translated multiple times, so a single error can have substantial effects on the pool of proteins. Transcription errors can also contribute to cellular noise, thereby influencing cell survival under stressful conditions, such as starvation or antibiotic stress. Implementing a method that captures transcription errors genome-wide, we measured the rates and spectra of transcription errors inEscherichia coliand in endosymbionts for which mutation and/or substitution rates are greatly elevated over those ofE. coli. Under all tested conditions, across all species, and even for different categories of RNA sequences (mRNA and rRNAs), there were no significant differences in rates of transcription errors, which ranged from 2.3 × 10−5per nucleotide in mRNA of the endosymbiontBuchnera aphidicolato 5.2 × 10−5per nucleotide in rRNA of the endosymbiontCarsonella ruddii. The similarity of transcription error rates in these bacterial endosymbionts to that inE. coli(4.63 × 10−5per nucleotide) is all the more surprising given that genomic erosion has resulted in the loss of transcription fidelity factors in bothBuchneraandCarsonella.

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