scholarly journals Determining the factors driving selective effects of new nonsynonymous mutations

2016 ◽  
Author(s):  
Christian D. Huber ◽  
Bernard Kim ◽  
Clare D. Marsden ◽  
Kirk E. Lohmueller
Keyword(s):  
Natural Populations ◽  
Evolutionary Genetics ◽  
Theoretical Models ◽  
Geometrical Model ◽  
Stabilizing Selection ◽  
Fundamental Parameter ◽  
Mutational Robustness ◽  
Medical Genomics ◽  
Multiple Phenotypes

AbstractThe distribution of fitness effects (DFE) of new mutations is a fundamental parameter in evolutionary genetics1–3. While theoretical models have emphasized the importance of distinct biological factors, such as protein folding4, back mutations5, species complexity6,7, and mutational robustness8 at determining the DFE, it remains unclear which of these models can describe the DFE in natural populations. Here, we show that the theoretical models make distinct predictions about how the DFE will differ between species. We further show that humans have a higher proportion of strongly deleterious mutations than Drosophila melanogaster. Comparing four categories of theoretical models, only Fisher’s Geometrical Model (FGM) is consistent with our data. FGM assumes that multiple phenotypes are under stabilizing selection, with the number of phenotypes defining a complexity of the organism. It suggests that long-term population size and cost of complexity drive the evolution of the DFE, with many implications for evolutionary and medical genomics.

scholarly journals Determining the factors driving selective effects of new nonsynonymous mutations

2017 ◽  
Vol 114 (17) ◽  
pp. 4465-4470 ◽  
Author(s):  
Christian D. Huber ◽  
Bernard Y. Kim ◽  
Clare D. Marsden ◽  
Kirk E. Lohmueller
Keyword(s):  
Natural Populations ◽  
Evolutionary Genetics ◽  
Theoretical Models ◽  
Geometrical Model ◽  
Stabilizing Selection ◽  
Mutational Robustness ◽  
Medical Genomics ◽  
Multiple Phenotypes ◽  
Comparative Population

The distribution of fitness effects (DFE) of new mutations plays a fundamental role in evolutionary genetics. However, the extent to which the DFE differs across species has yet to be systematically investigated. Furthermore, the biological mechanisms determining the DFE in natural populations remain unclear. Here, we show that theoretical models emphasizing different biological factors at determining the DFE, such as protein stability, back-mutations, species complexity, and mutational robustness make distinct predictions about how the DFE will differ between species. Analyzing amino acid-changing variants from natural populations in a comparative population genomic framework, we find that humans have a higher proportion of strongly deleterious mutations than Drosophila melanogaster. Furthermore, when comparing the DFE across yeast, Drosophila, mice, and humans, the average selection coefficient becomes more deleterious with increasing species complexity. Last, pleiotropic genes have a DFE that is less variable than that of nonpleiotropic genes. Comparing four categories of theoretical models, only Fisher’s geometrical model (FGM) is consistent with our findings. FGM assumes that multiple phenotypes are under stabilizing selection, with the number of phenotypes defining the complexity of the organism. Our results suggest that long-term population size and cost of complexity drive the evolution of the DFE, with many implications for evolutionary and medical genomics.

scholarly journals Natural selection can favor ratchet robustness over mutational robustness

2017 ◽  
Author(s):  
Yinghong Lan ◽  
Aaron Trout ◽  
Daniel Michael Weinreich ◽  
Christopher Scott Wylie
Keyword(s):  
Natural Selection ◽  
Natural Populations ◽  
Deleterious Mutations ◽  
Short Term ◽  
Mutational Robustness ◽  
Fundamental Interest ◽  
Fitness Advantage ◽  
Short And Long Term ◽  
Asexual Populations

AbstractThe vast majority of fitness-affecting mutations are deleterious. How natural populations evolve to cope is a question of fundamental interest. Previous studies have reported the evolution of mutational robustness, that is, natural selection favoring populations with less deleterious mutations. By definition, mutational robustness provides a short-term fitness advantage. However, this overlooks the fact that mutational robustness decreases finite asexual populations’ ability to purge recurrent deleterious mutations. Thus, mutational robustness also results in higher risk of long-term extinction by Muller’s ratchet. Here, we explore the tension between short- and long- term response to deleterious mutations. We first show that populations can resist the ratchet if either the selection coefficient or the ratio of beneficial to deleterious mutations increases as fitness declines. We designate these properties as ratchet robustness, which fundamentally reflects a negative feedback between mutation rate and the tendency to accumulate more mutations. We also find in simulations that populations can evolve ratchet robustness when challenged by deleterious mutations. We conclude that mutational robustness cannot be selected for in the long term, but it can be favored in the short-term, purely because of temporary fitness advantage. We also discuss other potential causes of mutational robustness in nature.

scholarly journals Mutation is a sufficient and robust predictor of genetic variation for mitotic spindle traits in C. elegans

2015 ◽  
Author(s):  
Reza Farhadifar ◽  
Jose Miguel Ponciano ◽  
Erik C Andersen ◽  
Daniel J Needleman ◽  
Charles F Baer
Keyword(s):  
Genetic Variation ◽  
Goodness Of Fit ◽  
Balancing Selection ◽  
Natural Populations ◽  
Evolutionary Genetics ◽  
Phenotypic Traits ◽  
Primary Role ◽  
Mutational Robustness ◽  
C Elegans ◽  
General Importance

Different types of phenotypic traits consistently exhibit different levels of genetic variation in natural populations. There are two potential explanations: either mutation produces genetic variation at different rates, or natural selection removes or promotes genetic variation at different rates. Whether mutation or selection is of greater general importance is a longstanding unresolved question in evolutionary genetics. Where the input of genetic variation by mutation differs between traits, it is usually uncertain whether the difference is the result of different mutational effects ("mutational robustness") or different numbers of underlying loci ("mutational target"), although conventional wisdom favors the latter. We report mutational variances (VM) for 19 traits related to the first mitotic cell division in C. elegans, and compare them to the standing genetic variances (VG) for the same suite of traits in a worldwide collection C. elegans. Two robust conclusions emerge. First, the mutational process is highly repeatable: the correlation between VM in two independent sets of mutation accumulation lines is ~0.9. Second, VM for a trait is a very good predictor of VG for that trait: the correlation between VM and VG is ~0.9. This result is predicted for a population at mutation-selection balance; it is not predicted if balancing selection plays a primary role in maintaining genetic variation. Goodness-of-fit of the data to two simple models of mutation suggest that differences in mutational effects may be a more important cause of differences in VM between traits than differences in the size of the mutational target.

scholarly journals Selection versus random drift: long–term polymorphism persistence in small populations (evidence and modelling)

1997 ◽  
Vol 352 (1351) ◽  
pp. 381-389 ◽  
Author(s):  
E. Nevo ◽  
V. Kirzhner ◽  
A. Beiles ◽  
A. Korol
Keyword(s):  
Theoretical Models ◽  
Mutation Rates ◽  
Stabilizing Selection ◽  
Small Populations ◽  
Isolated Populations ◽  
Random Drift ◽  
Subterranean Mammal ◽  
Or Gene ◽  
Additive Genes

Our data on a subterranean mammal, Spalax ehrenbergi , and other evidence, indicate that appreciable polymorphism can be preserved in small isolated populations consisting of several dozens of, or a hundred, individuals. Current theoretical models predict fast gene fixation in small panmictic populations without selection, mutation, or gene inflow. Using simple multilocus models, we demonstrate here that moderate stabilizing selection (with stable or fluctuating optimum) for traits controlled by additive genes could oppose random fixation in such isolates during thousands of generations. We also show that in selection–free models polymorphism persists only for a few hundred generations even under high mutation rates. Our multi-chromosome models challenge the hitchhiking hypothesis of polymorphism maintenance for many neutral loci due to close linkage with few selected loci.

Specific features of long-term domestication of australian crayfish Cherax quadricarinatus in conditions of the western part of Russian Federation

2018 ◽  
Vol 194 ◽  
pp. 188-192
Author(s):  
D. I. Shokasheva
Keyword(s):  
Natural Selection ◽  
Russian Federation ◽  
Natural Populations ◽  
Cherax Quadricarinatus ◽  
Local Environments ◽  
Local Species ◽  
Adaptive Ability

Natural populations of crayfish are in depression in Russia and local species are not cultivated. In this situation, experimental cultivation of allochtonous australian crayfish Cherax quadricarinatus is conducted. This species is distinguished by high reproductive abilities and good consumer properties. It has domesticated in Russia spontaneously and produced 9–10 generations in Astrakhan Region. Certain natural selection in the process of domestication provides adaptive ability of this species to local environments and its capabil­ity to reproduce a viable progeny, so there is no doubts in good prospects of its cultivation in industrial conditions.

Update on the Boundaries of the Curly Birch Range

2020 ◽  
pp. 9-21
Author(s):  
L.V. Vetchinnikova ◽  
◽  
A.F. Titov ◽  
◽  
Keyword(s):  
Population Size ◽  
Natural Populations ◽  
Forest Tree ◽  
Published Data ◽  
Population Approach ◽  
Key Factors ◽  
History Of ◽  
Individual Trees ◽  
Karelian Birch

The article reports on the application of the best known principles for mapping natural populations of curly (Karelian) birch Betula pendula Roth var. carelica (Mercklin) Hämet-Ahti – one of the most appealing representatives of the forest tree flora. Relying on the synthesis and analysis of the published data amassed over nearly 100 years and the data from own full-scale studies done in the past few decades almost throughout the area where curly birch has grown naturally, it is concluded that its range outlined in the middle of the 20th century and since then hardly revised is outdated. The key factors and reasons necessitating its revision are specified. Herewith it is suggested that the range is delineated using the population approach, and the key element will be the critical population size below which the population is no longer viable in the long term. This approach implies that the boundaries of the taxon range depend on the boundaries of local populations (rather than the locations of individual trees or small clumps of trees), the size of which should not be lower than the critical value, which is supposed to be around 100–500 trees for curly birch. A schematic map of the curly birch range delineated using this approach is provided. We specially address the problem of determining the minimum population size to secure genetic diversity maintenance. The advantages of the population approach to delineating the distribution range of curly birch with regard to its biological features are highlighted. The authors argue that it enables a more accurate delineation of the range; shows the natural evolutionary history of the taxon (although it is not yet officially recognized as a species) and its range; can be relatively easily updated (e.g. depending on the scope of reintroduction); should be taken into account when working on the strategy of conservation and other actions designed to maintain and regenerate this unique representative of the forest tree flora.

Emotion Dysregulation in Autism Spectrum Disorder

2018 ◽  
pp. 282-298
Author(s):  
Emily Neuhaus
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Educational Outcomes ◽  
Emotion Dysregulation ◽  
Research Priorities ◽  
Theoretical Models ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder

Autism spectrum disorder (ASD) is defined by deficits in social communication and interaction, and restricted and repetitive behaviors and interests. Although current diagnostic conceptualizations of ASD do not include emotional difficulties as core deficits, the disorder is associated with emotion dysregulation across the lifespan, with considerable implications for long-term psychological, social, and educational outcomes. The overarching goal of this chapter is to integrate existing knowledge of emotion dysregulation in ASD and identify areas for further investigation. The chapter reviews the prevalence and expressions of emotion dysregulation in ASD, discusses emerging theoretical models that frame emotion dysregulation as an inherent (rather than associated) feature of ASD, presents neurobiological findings and mechanisms related to emotion dysregulation in ASD, and identifies continuing controversies and resulting research priorities.

scholarly journals We’re Not That Choosy: Emerging Evidence of a Progression Bias in Romantic Relationships

2021 ◽  
pp. 108886832110258
Author(s):  
Samantha Joel ◽  
Geoff MacDonald
Keyword(s):  
Romantic Relationships ◽  
Mate Selection ◽  
Theoretical Models ◽  
Romantic Partners ◽  
Test Phase ◽  
Relationship Development ◽  
Cultural Narrative ◽  
Relationship Initiation ◽  
Relationship Decisions

Dating is widely thought of as a test phase for romantic relationships, during which new romantic partners carefully evaluate each other for long-term fit. However, this cultural narrative assumes that people are well equipped to reject poorly suited partners. In this article, we argue that humans are biased toward pro-relationship decisions—decisions that favor the initiation, advancement, and maintenance of romantic relationships. We first review evidence for a progression bias in the context of relationship initiation, investment, and breakup decisions. We next consider possible theoretical underpinnings—both evolutionary and cultural—that may explain why getting into a relationship is often easier than getting out of one, and why being in a less desirable relationship is often preferred over being in no relationship at all. We discuss potential boundary conditions that the phenomenon may have, as well as its implications for existing theoretical models of mate selection and relationship development.

Molecular biology of enzyme adaptations in higher eukaryotes

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 272-283 ◽  
Author(s):  
Donal A. Hickey ◽  
Bernhard F. Benkel ◽  
Charalambos Magoulas
Keyword(s):  
Molecular Biology ◽  
Tissue Specificity ◽  
Enzyme System ◽  
Direct Interaction ◽  
Evolutionary Genetics ◽  
Short Term ◽  
Eukaryotic Genes ◽  
Higher Eukaryotes ◽  
The Relationship

Multicellular eukaryotes have evolved complex homeostatic mechanisms that buffer the majority of their cells from direct interaction with the external environment. Thus, in these organisms long-term adaptations are generally achieved by modulating the developmental profile and tissue specificity of gene expression. Nevertheless, a subset of eukaryotic genes are still involved in direct responses to environmental fluctuations. It is the adaptative responses in the expression of these genes that buffers many other genes from direct environmental effects. Both microevolutionary and macroevolutionary patterns of change in the structure and regulation of such genes are illustrated by the sequences encoding α-amylases. The molecular biology and evolution of α-amylases in Drosophila and other higher eukaryotes are presented. The amylase system illustrates the effects of both long-term and short-term natural selection, acting on both the structural and regulatory components of a gene–enzyme system. This system offers an opportunity for linking evolutionary genetics to molecular biology, and it allows us to explore the relationship between short-term microevolutionary changes and long-term adaptations.Key words: gene regulation, molecular evolution, eukaryotes, Drosophila, amylase.

scholarly journals On the mod resc Model and the Evolution of Wolbachia Compatibility Types

Genetics ◽  
2001 ◽  
Vol 159 (4) ◽  
pp. 1415-1422 ◽  
Author(s):  
Sylvain Charlat ◽  
Claire Calmet ◽  
Hervé Merçot
Keyword(s):  
Cytoplasmic Incompatibility ◽  
Natural Populations ◽  
Evolutionary Process ◽  
Embryonic Mortality ◽  
Step Process ◽  
Zygote Development ◽  
Specific Manner

Abstract Cytoplasmic incompatibility (CI) is induced by the endocellular bacterium Wolbachia. It results in an embryonic mortality occurring when infected males mate with uninfected females. The mechanism involved is currently unknown, but the mod resc model allows interpretation of all observations made so far. It postulates the existence of two bacterial functions: modification (mod) and rescue (resc). The mod function acts in the males' germline, before Wolbachia are shed from maturing sperm. If sperm is affected by mod, zygote development will fail unless resc is expressed in the egg. Interestingly, CI is also observed in crosses between infected males and infected females when the two partners bear different Wolbachia strains, demonstrating that mod and resc interact in a specific manner: Two Wolbachia strains are compatible with each other only if they harbor the same compatibility type. Here we focus on the evolutionary process involved in the emergence of new compatibility types from ancestral ones. We argue that new compatibility types are likely to evolve under a wider range of conditions than previously thought, through a two-step process. First, new mod variants can arise by mutation and spread by drift. This is possible because mod is expressed in males and Wolbachia is transmitted by females. Second, once such a mod variant achieves a certain frequency, it can create the conditions for the deterministic invasion of a new resc variant, allowing the invasion of a new mod resc pair. Furthermore, we show that a stable polymorphism might be maintained in natural populations, allowing the long-term existence of “suicidal” Wolbachia strains.

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