Mutational and Selective Processes Involved in Evolution during Bacterial Range Expansions

AbstractBacterial populations have been shown to accumulate deleterious mutations during spatial expansions that overall decrease their fitness and ability to grow. However, it is unclear if and how they can respond to selection in face of this mutation load. We examine here if artificial selection can counteract the negative effects of range expansions. We investigated the molecular evolution of 20 lines (SEL) selected for fast expansions and compared them to 20 lines without artificial selection (CONTROL). We find that all 20 SEL lines have been able to increase their expansion speed relative to the ancestral line, unlike CONTROL lines, showing that enough beneficial mutations are produced during spatial expansions to counteract the negative effect of expansion load. Importantly, SEL and CONTROL lines have similar numbers of mutations indicating that they evolved for the same number of generations and that increased fitness is not due to a purging of deleterious mutations. We find that loss of function (LOF) mutations are better at explaining the increased expansion speed of SEL lines than non-synonymous mutations or a combination of the two. Interestingly, most LOF mutations are found in simple sequence repeats located in genes involved in gene regulation and gene expression. We postulate that such potentially reversible mutations could play a major role in the rapid adaptation of bacteria to changing environmental conditions by shutting down expensive genes and adjusting gene expression.Author SummaryWe investigated if strong artificial selection for fast expansion can counteract the negative effects of range expansion which had been shown to lead to an accumulation of deleterious mutations. This experiments showed that i) an increase in expansion speed could occur if bacteria were selected from the largest protruding sectors, and ii) that artificially selected bacterial lines accumulated about the same number of mutations than simply expanding line suggesting that the observed increased fitness is not due to increased purifying selection where deleterious mutations would have been removed in fast growing lines. We find that loss of function (LOF) mutations are best explaining the observed increased expansion speed in selected lines. These mutations, which are known to play an important role in adaptive processes in bacterial populations, frequently consist in small insertion-deletions in simple sequence repeats, and are thus relatively easily reversible. They could thus act as switches that can reversibly shut down genes. Our results therefore suggest that shutting down expensive genes and adjusting gene expression are important for adaptive processes during range expansion.

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Context-dependent gene expression: cis-acting negative effects of specific procaryotic plasmid sequences on eucaryotic genes.

Molecular and Cellular Biology ◽

10.1128/mcb.7.4.1563 ◽

1987 ◽

Vol 7 (4) ◽

pp. 1563-1567 ◽

Cited By ~ 27

Author(s):

D O Peterson ◽

K K Beifuss ◽

K L Morley

Keyword(s):

Gene Expression ◽

Dna Replication ◽

Transient Expression ◽

Negative Effects ◽

Sequence Element ◽

Negative Element ◽

Cis Acting ◽

Pbr322 Dna ◽

Negative Effect ◽

Context Dependent

A sequence element within pBR322 DNA mediates a cis-acting negative effect on expression from eucaryotic genes in transient expression assays. The negative element overlaps with sequences that inhibit DNA replication, but its effect is observed in the absence of detectable replication of transfected DNA.

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Dominant negative effects of SCN5A missense variants

10.1101/2021.09.22.461398 ◽

2021 ◽

Author(s):

Matthew J O'Neill ◽

Ayesha Muhammad ◽

Bian Li ◽

Yuko Wada ◽

Lynn Hall ◽

...

Keyword(s):

Protein Product ◽

Dominant Negative ◽

Dominant Negative Effect ◽

Loss Of Function ◽

Negative Effects ◽

Population Database ◽

Peak Current ◽

Missense Variants ◽

Cardiac Sodium Channel ◽

Negative Effect

Introduction: Up to 30% of patients with Brugada Syndrome (BrS) carry loss-of-function (LoF) variants in the cardiac sodium channel gene SCN5A. Recent studies have suggested that the SCN5A protein product NaV1.5 can form dimers and exert dominant negative effects. Methods: We identified 35 LoF variants (<10% peak current compared to wild type (WT)) and 15 partial LoF variants (10-50% peak current compared to WT) that we assessed for dominant negative behavior. SCN5A variants were studied in HEK293T cells alone or in heterozygous co-expression with WT SCN5A using automated patch clamp. To assess clinical risk, we compared the prevalence of dominant negative vs. putative haploinsufficient (frameshift/splice site) variants in a BrS case consortium and the gnomAD population database. Results: In heterozygous expression with WT, 32/35 LoF variants and 6/15 partial LoF showed reduction to <75% of WT-alone peak INa, demonstrating a dominant negative effect. Carriers of dominant negative LoF missense variants had an enriched disease burden compared to putative haploinsufficient variant carriers (2.7-fold enrichment in BrS cases, p=0.019). Conclusions: Most SCN5A missense LoF variants exert a dominant negative effect. Cohort analyses reveal that this class of variant confers an especially high burden of BrS.

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Deleterious mutations show increasing negative effects with age in Drosophila melanogaster

BMC Biology ◽

10.1186/s12915-020-00858-5 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Martin I. Brengdahl ◽

Christopher M. Kimber ◽

Phoebe Elias ◽

Josephine Thompson ◽

Urban Friberg

Keyword(s):

Drosophila Melanogaster ◽

Genetic Architecture ◽

Deleterious Mutations ◽

Negative Effects ◽

Evolutionary Theories ◽

Theories Of Aging ◽

Specific Effects ◽

Rate Of Increase ◽

Negative Effect ◽

Evolution Of Aging

Abstract Background In order for aging to evolve in response to a declining strength of selection with age, a genetic architecture that allows for mutations with age-specific effects on organismal performance is required. Our understanding of how selective effects of individual mutations are distributed across ages is however poor. Established evolutionary theories assume that mutations causing aging have negative late-life effects, coupled to either positive or neutral effects early in life. New theory now suggests evolution of aging may also result from deleterious mutations with increasing negative effects with age, a possibility that has not yet been empirically explored. Results To directly test how the effects of deleterious mutations are distributed across ages, we separately measure age-specific effects on fecundity for each of 20 mutations in Drosophila melanogaster. We find that deleterious mutations in general have a negative effect that increases with age and that the rate of increase depends on how deleterious a mutation is early in life. Conclusions Our findings suggest that aging does not exclusively depend on genetic variants assumed by the established evolutionary theories of aging. Instead, aging can result from deleterious mutations with negative effects that amplify with age. If increasing negative effect with age is a general property of deleterious mutations, the proportion of mutations with the capacity to contribute towards aging may be considerably larger than previously believed.

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Recency negativity: Newer food crops are evaluated less favorably

10.31234/osf.io/k2bw7 ◽

2020 ◽

Author(s):

Yoel Inbar ◽

Jordan Phelps ◽

Paul Rozin

Keyword(s):

Genetic Engineering ◽

Artificial Selection ◽

New Technologies ◽

Meta Analysis ◽

Food Crops ◽

Negative Effects ◽

Conventional Breeding ◽

Negative Effect ◽

Within Subjects

Food crops produced by new technologies such as genetic engineering are widely opposed (Gaskell, Bauer, Durant & Allum, 1999; Scott, Inbar, Wirz, Brossard & Rozin, 2018). Here, we examine one reason for this opposition: recency. More recently-developed crops are evaluated less favorably, whether they are produced by artificial selection (i.e., conventional breeding), natural or man-made irradiation, or genetic engineering. Negative effects of recency persist in a within-subjects design where people are able to explicitly compare crops developed at different times, and an internal meta-analysis shows that the negative effect of recency is robust across measures and stimuli. These results have implications for the evaluation of crops produced using new modification techniques, including the widespread opposition to genetic engineering.

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Dissection of the mutation accumulation process during bacterial range expansions

10.21203/rs.2.20228/v1 ◽

2020 ◽

Author(s):

Lars Bosshard ◽

Stephan Peischl ◽

Martin Ackermann ◽

Laurent Excoffier

Keyword(s):

Colony Size ◽

Evolutionary Dynamics ◽

Early Stage ◽

Colony Growth ◽

Spatial Expansion ◽

Deleterious Mutations ◽

Temporal Perspective ◽

Linear Change ◽

Beneficial Mutations ◽

Bacterial Populations

Abstract Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes.Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days (∼1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. Even though the colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, colony size remains almost constant at the beginning of the experiment and then decreases after ∼12 days of evolution. We also find that beneficial mutations are enriched in flagella genes, genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process.Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole gnome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion.

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Context-dependent gene expression: cis-acting negative effects of specific procaryotic plasmid sequences on eucaryotic genes

Molecular and Cellular Biology ◽

10.1128/mcb.7.4.1563-1567.1987 ◽

1987 ◽

Vol 7 (4) ◽

pp. 1563-1567

Author(s):

D O Peterson ◽

K K Beifuss ◽

K L Morley

Keyword(s):

Gene Expression ◽

Dna Replication ◽

Transient Expression ◽

Negative Effects ◽

Sequence Element ◽

Negative Element ◽

Cis Acting ◽

Pbr322 Dna ◽

Negative Effect ◽

Context Dependent

A sequence element within pBR322 DNA mediates a cis-acting negative effect on expression from eucaryotic genes in transient expression assays. The negative element overlaps with sequences that inhibit DNA replication, but its effect is observed in the absence of detectable replication of transfected DNA.

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Actin-Related Protein 4 Interacts with PIE1 and Regulates Gene Expression in Arabidopsis

Genes ◽

10.3390/genes12040520 ◽

2021 ◽

Vol 12 (4) ◽

pp. 520

Author(s):

Wenfeng Nie ◽

Jinyu Wang

Keyword(s):

Gene Expression ◽

Plant Growth ◽

Chromatin Remodeling ◽

Leaf Size ◽

Early Flowering ◽

Physical Interaction ◽

Loss Of Function ◽

Single Nucleotide Change ◽

Chromatin Remodeling Complex ◽

Related Proteins

As essential structural components of ATP-dependent chromatin-remodeling complex, the nucleolus-localized actin-related proteins (ARPs) play critical roles in many biological processes. Among them, ARP4 is identified as an integral subunit of chromatin remodeling complex SWR1, which is conserved in yeast, humans and plants. It was shown that RNAi mediated knock-down of Arabidopsis thaliana ARP4 (AtARP4) could affect plant development, specifically, leading to early flowering. However, so far, little is known about how ARP4 functions in the SWR1 complex in plant. Here, we identified a loss-of-function mutant of AtARP4 with a single nucleotide change from glycine to arginine, which had significantly smaller leaf size. The results from the split luciferase complementation imaging (LCI) and yeast two hybrid (Y2H) assays confirmed its physical interaction with the scaffold and catalytic subunit of SWR1 complex, photoperiod-independent early flowering 1 (PIE1). Furthermore, mutation of AtARP4 caused altered transcription response of hundreds of genes, in which the number of up-regulated differentially expressed genes (DEGs) was much larger than those down-regulated. Although most DEGs in atarp4 are related to plant defense and response to hormones such as salicylic acid, overall, it has less overlapping with other swr1 mutants and the hta9 hta11 double-mutant. In conclusion, our results reveal that AtARP4 is important for plant growth and such an effect is likely attributed to its repression on gene expression, typically at defense-related loci, thus providing some evidence for the coordination of plant growth and defense, while the regulatory patterns and mechanisms are distinctive from other SWR1 complex components.

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Harmful mutation load in the mitochondrial genomes of cattle breeds

BMC Research Notes ◽

10.1186/s13104-021-05664-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Sankar Subramanian

Keyword(s):

Population Size ◽

Artificial Selection ◽

Deleterious Mutation ◽

Genetic Diseases ◽

Mitochondrial Genomes ◽

Deleterious Mutations ◽

Founder Population ◽

Mutation Load ◽

Effective Population ◽

Cattle Breeds

Abstract Objective Domestication of wild animals results in a reduction in the effective population size, and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to the accumulation of deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using mitochondrial genome data from 364 animals belonging to 18 cattle breeds of the world. Results Our analysis revealed more than a fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the breed age and the proportion of deleterious amino acid-changing polymorphisms. This suggests a proportionally higher deleterious SNPs in young breeds compared to older breeds. Our results highlight the magnitude of difference in the deleterious mutations present in the mitochondrial genomes of various breeds. The results of this study could be useful in predicting the rate of incidence of genetic diseases in different breeds.

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Asthma patients experience increased symptoms of anxiety, depression and fear during the COVID-19 pandemic

Chronic Respiratory Disease ◽

10.1177/14799731211029658 ◽

2021 ◽

Vol 18 ◽

pp. 147997312110296

Author(s):

Geertje M de Boer ◽

Laura Houweling ◽

Rudi W Hendriks ◽

Jan H Vercoulen ◽

Gerdien A Tramper-Stranders ◽

...

Keyword(s):

Online Survey ◽

Anxiety And Depression ◽

Negative Effects ◽

Cross Sectional ◽

Healthcare Facilities ◽

Care Workers ◽

Asthma Patients ◽

Negative Effect ◽

Patients Experience ◽

Anxiety Depression

Population studies showed a decrease in psychological wellbeing during the COVID-19 pandemic. Asthma is associated with a negative effect on anxiety and depression, which might worsen during the COVID-19 lockdown. The aim of the study was to compare fear, anxiety and depression between asthma patients and patients wit hout asthma pre-COVID-19 and during COVID-19 pandemic. This study compares fear, anxiety and depression in asthma patients and controls between pre-COVID-19 and during COVID-19 lockdown with a cross-sectional online survey. Participants were invited to fill out several questionnaires pertaining to fear, anxiety, depression, asthma control and quality of life. Asthma patients (N = 37) displayed, during the course of the pandemic, a clinically relevant increase in anxiety (3.32 ± 2.95 vs. 6.68 ± 3.78; p < 0.001) and depression (1.30 ± 1.15 vs. 3.65 ± 3.31; p < 0.001), according to the hospital anxiety and depression levels (HADS) compared to pre-COVID-19 assessment. This was not seen in controls. Also, asthma patients displayed more anxiety about acquiring COVID-19 disease compared to controls ((5.11 ± 1.99 vs. 3.50 ± 2.79), p = 0.006). Patients with asthma experienced an increase in anxiety and depression levels and were more afraid of acquiring COVID-19 disease compared to controls. Also, patients with asthma were more likely to avoid healthcare facilities due to fear of acquiring COVID-19 disease compared to controls. Therefore, we advise health care workers to address these possible negative effects on mental health by phone or e-consults.

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