scholarly journals Deleterious mutation accumulation and the long-term fate of chromosomal inversions

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009411
Author(s):  
Emma L. Berdan ◽  
Alexandre Blanckaert ◽  
Roger K. Butlin ◽  
Claudia Bank
Keyword(s):  
Adaptive Evolution ◽  
Simulation Study ◽  
Feedback Loop ◽  
Deleterious Mutation ◽  
Adaptive Divergence ◽  
Deleterious Mutations ◽  
Dynamic Features ◽  
Chromosomal Inversions

Chromosomal inversions contribute widely to adaptation and speciation, yet they present a unique evolutionary puzzle as both their allelic content and frequency evolve in a feedback loop. In this simulation study, we quantified the role of the allelic content in determining the long-term fate of the inversion. Recessive deleterious mutations accumulated on both arrangements with most of them being private to a given arrangement. This led to increasing overdominance, allowing for the maintenance of the inversion polymorphism and generating strong non-adaptive divergence between arrangements. The accumulation of mutations was mitigated by gene conversion but nevertheless led to the fitness decline of at least one homokaryotype under all considered conditions. Surprisingly, this fitness degradation could be permanently halted by the branching of an arrangement into multiple highly divergent haplotypes. Our results highlight the dynamic features of inversions by showing how the non-adaptive evolution of allelic content can play a major role in the fate of the inversion.

scholarly journals Deleterious Mutation Accumulation and the Long-Term Fate of Chromosomal Inversions

2019 ◽  
Author(s):  
Emma L. Berdan ◽  
Alexandre Blanckaert ◽  
Roger K. Butlin ◽  
Claudia Bank
Keyword(s):  
Selective Advantage ◽  
Inversion Polymorphism ◽  
Adaptive Divergence ◽  
Deleterious Mutations ◽  
Dynamic Features ◽  
Chromosomal Inversions ◽  
Recessive Mutations ◽  
Standard Arrangement

AbstractChromosomal inversions contribute widely to adaptation and speciation, yet they present a unique evolutionary puzzle as both their allelic content and frequency evolve in a feedback loop. In this simulation study, we quantified the role of the allelic content in determining the long-term fate of the inversion. Recessive deleterious mutations accumulated on both arrangements with most of them being private to a given arrangement. This led to increasing overdominance, allowing for the maintenance of the inversion polymorphism and generating strong non-adaptive divergence between arrangements. The accumulation of mutations was mitigated by gene conversion but nevertheless led to the fitness decline of at least one homokaryotype under all considered conditions. Surprisingly, this fitness degradation could be permanently halted by the branching of an arrangement into multiple highly divergent haplotypes. Our results highlight the dynamic features of inversions by showing how the non-adaptive evolution of allelic content can play a major role in the fate of the inversion.Author SummaryA chromosomal inversion is a segment of the chromosome that is flipped (inverted arrangement) relative to the normal orientation (standard arrangement). Such structural mutations may facilitate evolutionary processes such as adaptation and speciation, because reduced recombination in inverted regions allows beneficial combinations of alleles to behave as a “single unit”. This locally reduced recombination can have major consequences for the evolution of the allelic content inside the inversion. We used simulations to investigate some of these consequences. Inverted regions tended to accumulate more deleterious recessive mutations than the rest of the genome, which decreased the fitness of homokarotypes (individuals with two copies of the same arrangement). This led to a strong selective advantage for heterokaryotypes (individuals with one copy of each arrangement), maintaining the inversion polymorphism in the population. The accumulation of deleterious mutations also resulted in strong divergence between arrangements. We occasionally observed an arrangement that diverged into a small number of highly differentiated haplotypes, stopping the fitness decrease in homokaryotypes. Our results highlight the dynamic features of inversions by showing how the evolution of allelic content can greatly affect the fate of an inversion.

scholarly journals Experiments on the role of deleterious mutations as stepping stones in adaptive evolution

2013 ◽  
Vol 110 (34) ◽  
pp. E3171-E3178 ◽  
Author(s):  
Arthur W. Covert ◽  
Richard E. Lenski ◽  
Claus O. Wilke ◽  
Charles Ofria
Keyword(s):  
Adaptive Evolution ◽  
Deleterious Mutations ◽  
Stepping Stones

scholarly journals Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop

2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Autocrine Signaling ◽  
Positive Feedback Loop ◽  
Short Term Plasticity ◽  
Extracellular Signaling ◽  
Presynaptic Protein ◽  
Long Term Facilitation

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.

scholarly journals On the origin of species: insights from the ecological genomics of lake whitefish

2010 ◽  
Vol 365 (1547) ◽  
pp. 1783-1800 ◽  
Author(s):  
Louis Bernatchez ◽  
Sébastien Renaut ◽  
Andrew R. Whiteley ◽  
Nicolas Derome ◽  
Julie Jeukens ◽  
...  
Keyword(s):  
Research Programme ◽  
Adaptive Divergence ◽  
Population Divergence ◽  
Ecological Genomics ◽  
Model Species ◽  
Sequencing Technologies ◽  
Sympatric Forms ◽  
Genomic Tools

In contrast to the large amount of ecological information supporting the role of natural selection as a main cause of population divergence and speciation, an understanding of the genomic basis underlying those processes is in its infancy. In this paper, we review the main findings of a long-term research programme that we have been conducting on the ecological genomics of sympatric forms of whitefish ( Coregonus spp.) engaged in the process of speciation. We present this system as an example of how applying a combination of approaches under the conceptual framework of the theory of adaptive radiation has yielded substantial insight into evolutionary processes in a non-model species. We also discuss how the joint use of recent biotechnological developments will provide a powerful means to address issues raised by observations made to date. Namely, we present data illustrating the potential offered by combining next generation sequencing technologies with other genomic approaches to reveal the genomic bases of adaptive divergence and reproductive isolation. Given increasing access to these new genomic tools, we argue that non-model species studied in their ecological context such as whitefish will play an increasingly important role in generalizing knowledge of speciation.

scholarly journals A deleterious mutation-sheltering theory for the evolution of sex chromosomes and supergenes

2021 ◽  
Author(s):  
Paul Jay ◽  
Tatiana Giraud ◽  
Emilie Tezenas
Keyword(s):  
Mathematical Modeling ◽  
Sex Chromosomes ◽  
Deleterious Mutation ◽  
Stochastic Simulations ◽  
Recessive Mutation ◽  
Deleterious Mutations ◽  
Evolution Of Sex ◽  
Mutation Load ◽  
Recombination Suppression ◽  
Chromosomal Inversions

Many organisms have sex chromosomes with large non-recombining regions having expanded stepwise, the reason why being still poorly understood. Theories proposed so far rely on differences between sexes but are poorly supported by empirical data and cannot account for the stepwise suppression of recombination around sex chromosomes in organisms without sexual dimorphism. We show here, by mathematical modeling and stochastic simulations, that recombination suppression in sex chromosomes can evolve simply because it shelters recessive deleterious mutations, which are ubiquitous in genomes. The permanent heterozygosity of sex-determining alleles protects linked chromosomal inversions against expression of their recessive mutation load, leading to an accumulation of inversions around these loci, as observed in nature. We provide here a testable and widely applicable theory to explain the evolution of sex chromosomes and of supergenes in general.

scholarly journals A Computer Simulation Study of Anatomy Induced Drift of Spiral Waves in the Human Atrium

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Sanjay R. Kharche ◽  
Irina V. Biktasheva ◽  
Gunnar Seemann ◽  
Henggui Zhang ◽  
Vadim N. Biktashev
Keyword(s):  
Wall Thickness ◽  
Simulation Study ◽  
Sudden Change ◽  
Spiral Wave ◽  
Spiral Waves ◽  
Human Atrium ◽  
Atrial Wall ◽  
Anatomical Structures

The interaction of spiral waves of excitation with atrial anatomy remains unclear. This simulation study isolates the role of atrial anatomical structures on spiral wave spontaneous drift in the human atrium. We implemented realistic and idealised 3D human atria models to investigate the functional impact of anatomical structures on the long-term (∼40 s) behaviour of spiral waves. The drift of a spiral wave was quantified by tracing its tip trajectory, which was correlated to atrial anatomical features. The interaction of spiral waves with the following idealised geometries was investigated: (a) a wedge-like structure with a continuously varying atrial wall thickness; (b) a ridge-like structure with a sudden change in atrial wall thickness; (c) multiple bridge-like structures consisting of a bridge connected to the atrial wall. Spiral waves drifted from thicker to thinner regions and along ridge-like structures. Breakthrough patterns caused by pectinate muscles (PM) bridges were also observed, albeit infrequently. Apparent anchoring close to PM-atrial wall junctions was observed. These observations were similar in both the realistic and the idealised models. We conclude that spatially altering atrial wall thickness is a significant cause of drift of spiral waves. PM bridges cause breakthrough patterns and induce transient anchoring of spiral waves.

scholarly journals Estimation of Deleterious-Mutation Parameters in Natural Populations

Genetics ◽  
1996 ◽  
Vol 144 (1) ◽  
pp. 349-360 ◽  
Author(s):  
Hong-Wen Deng ◽  
Michael Lynch
Keyword(s):  
Genetic Variance ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Breeding Systems ◽  
Deleterious Mutations ◽  
Empirical Estimates ◽  
Mean Fitness ◽  
The Mean ◽  
New Mutations

Abstract The rate and average effects of spontaneous deleterious mutations are important determinants of the evolution of breeding systems and of the vulnerability of small populations to extinction. Nevertheless, few attempts have been made to estimate the properties of such mutations, and those studies that have been performed have been extremely labor intensive, relying on long-term, laboratory mutation-accumulation experiments. We present an alternative to the latter approach. For populations in which the genetic variance for fitness is a consequence of selection-mutation balance, the mean fitness and genetic variance of fitness in outbred and inbred generations can be expressed as simple functions of the genomic mutation rate, average homozygous effect and average dominance coefficient of new mutations. Using empirical estimates for the mean and genetic variance of fitness, these expressions can then be solved to obtain joint estimates of the deleterious-mutation parameters. We employ computer simulations to evaluate the degree of bias of the estimators and present some general recommendations on the application of the technique. Our procedures provide some hope for obtaining estimates of the properties of deleterious mutations from a wide phylogenetic range of species as well as a mechanism for testing the validity of alternative models for the maintenance of genetic variance for fitness.

Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation

2019 ◽  
Vol 77 (3) ◽  
Author(s):  
Tomás Villaseñor ◽  
Edgardo Madrid-Paulino ◽  
Rafael Maldonado-Bravo ◽  
Leonor Pérez-Martínez ◽  
Gustavo Pedraza-Alva
Keyword(s):  
Mycobacterium Bovis ◽  
Feedback Loop ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Cytokine Gene Expression ◽  
Mycobacterium Bovis Bcg ◽  
Adaptive Immune

ABSTRACT Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood. Here, we report that Mycobacterium bovis BCG promotes IL-10 expression and cytokine production by establishing a SYK/PKCα/β positive feedback loop that leads to STAT3 activation.

scholarly journals The importance of alternative splicing in adaptive evolution

2021 ◽  
Author(s):  
Pooja Singh ◽  
Ehsan Pashay Ahi
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Adaptive Evolution ◽  
Adaptive Divergence ◽  
Mrna Isoforms ◽  
Evolutionary Transitions ◽  
Splice Variation ◽  
Gene Regulatory ◽  
Splice Forms

Although alternative splicing is a ubiquitous gene regulatory mechanism in plants and animals, its contribution to evolutionary transitions is understudied. Splicing enables different mRNA isoforms to be generated from the same gene, expanding transcriptomic and proteomic diversity. While the role of gene expression in adaptive evolution is widely accepted, biologists still debate the functional impact of alternative isoforms on phenotype. In light of recent empirical research linking splice variation to ecological adaptations, we propose that alternative splicing is an important substrate for adaptive evolution and speciation, particularly at short timescales. We synthesise what is known about the role of splicing in adaptive evolution. We discuss the contribution of standing splice variation to phenotypic plasticity and how hybridisation can produce novel splice forms. Going forwards, we propose that splicing be included as a standard analysis alongside gene expression analysis so we can better understand of how splicing contributes to adaptive divergence at the micro- and macroevolutionary levels.

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