scholarly journals Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients

2016 ◽  
Vol 29 (3) ◽  
pp. 583-593 ◽  
Author(s):  
S. A. Kraemer ◽  
A. D. Morgan ◽  
R. W. Ness ◽  
P. D. Keightley ◽  
N. Colegrave
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Stress Gradients ◽  
Fitness Effects ◽  
New Mutations

scholarly journals Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients

2015 ◽  
Author(s):  
Susanne A Kraemer ◽  
Andrew D Morgan ◽  
Robert W Ness ◽  
Peter D Keightley ◽  
Nick Colegrave
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Genetic Load ◽  
Relative Fitness ◽  
Stress Gradients ◽  
Population Extinction ◽  
Fitness Effects ◽  
Generation Times ◽  
Fitness Measures ◽  
Detection Of Stress ◽  
Stress Dependent

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress-dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algae Chlamydomonas reinhardtii that accumulated mutations in the near absence of selection for approximately 1,000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress as well as to the genetic background. The detection of stress-dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies.

scholarly journals The distribution of mutational effects on fitness in Caenorhabditis elegans inferred from standing genetic variation

2020 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Stefan Zdraljevic ◽  
Daniel E. Cook ◽  
Asher D. Cutter ◽  
Erik C. Andersen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Population Size ◽  
Genomic Structure ◽  
Random Mating ◽  
Population Substructure ◽  
C Elegans ◽  
Fitness Effects ◽  
Self Fertilization ◽  
New Mutations

ABSTRACTThe distribution of fitness effects for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the distribution of fitness effects (DFE) from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, and non-random mating. Although inference methods aim to control for population size changes, the influence of non-random mating remains incompletely understood, despite being a common feature of many species. We report the distribution of fitness effects estimated from 326 genomes of Caenorhabditis elegans, a nematode roundworm with a high rate of self-fertilization. We evaluate the robustness of DFE inferences using simulated data that mimics the genomic structure and reproductive life history of C. elegans. Our observations demonstrate how the combined influence of self-fertilization, genome structure, and natural selection can conspire to compromise estimates of the DFE from extant polymorphisms. These factors together tend to bias inferences towards weakly deleterious mutations, making it challenging to have full confidence in the inferred DFE of new mutations as deduced from standing genetic variation in species like C. elegans. Improved methods for inferring the distribution of fitness effects are needed to appropriately handle strong linked selection and selfing. These results highlight the importance of understanding the combined effects of processes that can bias our interpretations of evolution in natural populations.

The distribution of fitness effects of new mutations

2007 ◽  
Vol 8 (8) ◽  
pp. 610-618 ◽  
Author(s):  
Adam Eyre-Walker ◽  
Peter D. Keightley
Keyword(s):  
Fitness Effects ◽  
New Mutations

scholarly journals The distribution of fitness effects of new beneficial mutations in Pseudomonas fluorescens

2010 ◽  
Vol 7 (1) ◽  
pp. 98-100 ◽  
Author(s):  
Michael J. McDonald ◽  
Tim F. Cooper ◽  
Hubertus J. E. Beaumont ◽  
Paul B. Rainey
Keyword(s):  
Natural Selection ◽  
Normal Distribution ◽  
Pseudomonas Fluorescens ◽  
Genetic Architecture ◽  
Rank Order ◽  
Detailed Knowledge ◽  
Theoretical Studies ◽  
Fitness Effects ◽  
Reference Type ◽  
New Mutations

Theoretical studies of adaptation emphasize the importance of understanding the distribution of fitness effects (DFE) of new mutations. We report the isolation of 100 adaptive mutants—without the biasing influence of natural selection—from an ancestral genotype whose fitness in the niche occupied by the derived type is extremely low. The fitness of each derived genotype was determined relative to a single reference type and the fitness effects found to conform to a normal distribution. When fitness was measured in a different environment, the rank order changed, but not the shape of the distribution. We argue that, even with detailed knowledge of the genetic architecture underpinning the adaptive types (as is the case here), the DFEs remain unpredictable, and we discuss the possibility that general explanations for the shape of the DFE might not be possible in the absence of organism-specific biological details.

scholarly journals What does the Distribution of Fitness Effects of new mutations (DFE) reflect? Insights from plants

2021 ◽  
Author(s):  
Jun Chen ◽  
Thomas Bataillon ◽  
Sylvain Glémin ◽  
Martin Lascoux
Keyword(s):  
Fitness Effects ◽  
New Mutations

scholarly journals The distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii inferred using frequency changes under experimental evolution

2021 ◽  
Author(s):  
Katharina B. Böndel ◽  
Toby Samuels ◽  
Rory J. Craig ◽  
Rob W. Ness ◽  
Nick Colegrave ◽  
...  
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Experimental Evolution ◽  
Spontaneous Mutations ◽  
Negative Effects ◽  
Serial Transfer ◽  
Fitness Effects ◽  
Markov Chain Method ◽  
Bayesian Monte Carlo ◽  
High Fraction ◽  
Frequency Changes

The distribution of fitness effects (DFE) for new mutations is fundamental for many aspects of population and quantitative genetics. In this study, we have inferred the DFE in the single-celled alga Chlamydomonas reinhardtii by estimating changes in the frequencies of 254 spontaneous mutations under experimental evolution and equating the frequency changes of linked mutations with their selection coefficients. We generated seven populations of recombinant haplotypes by crossing seven independently derived mutation accumulation lines carrying an average of 36 mutations in the homozygous state to a mutation-free strain of the same genotype. We then allowed the populations to evolve under natural selection in the laboratory by serial transfer in liquid culture. We observed substantial and repeatable changes in the frequencies of many groups of linked mutations, and, surprisingly, as many mutations were observed to increase as decrease in frequency. We developed a Bayesian Monte Carlo Markov Chain method to infer the DFE. This computes the likelihood of the observed distribution of changes of frequency, and obtains the posterior distribution of the selective effects of individual mutations, while assuming a two-sided gamma distribution of effects. We infer that the DFE is a highly leptokurtic distribution, and that approximately equal proportions of mutations have positive and negative effects on fitness. This result is consistent with what we have observed in previous work on a different C. reinhardtii strain, and suggests that a high fraction of new spontaneously arisen mutations are advantageous in a simple laboratory environment.

scholarly journals The evolutionary impacts of synonymous mutations

2021 ◽  
Author(s):  
Deepa Agashe
Keyword(s):  
Synonymous Codon ◽  
Analytical Framework ◽  
Synonymous Mutations ◽  
Fitness Effects ◽  
Distinct Category ◽  
Dramatic Shift ◽  
Evolutionary Consequences ◽  
New Mutations

During the 50 years since the genetic code was cracked, our understanding of the evolutionary consequences of synonymous mutations has undergone a dramatic shift. Synonymous codon changes were initially considered selectively neutral, and as such, exemplars of evolution via genetic drift. However, the pervasive and non-negligible fitness impacts of synonymous mutations are now clear across organisms. Despite the accumulated evidence, it remains challenging to incorporate the effects of synonymous changes in studies of selection, because the existing analytical framework was built with a focus on the fitness effects of nonsynonymous mutations. In this chapter, I trace the development of this topic and discuss the evidence that gradually transformed our thinking about the role of synonymous mutations in evolution. I suggest that our evolutionary framework should encompass the impacts of all mutations on various forms of information transmission. Folding synonymous mutations into a common distribution – rather than setting them apart as a distinct category – will allow a more complete and cohesive picture of the evolutionary consequences of new mutations.

scholarly journals Inferring Parameters of the Distribution of Fitness Effects of New Mutations When Beneficial Mutations Are Strongly Advantageous and Rare

2020 ◽  
Vol 10 (7) ◽  
pp. 2317-2326 ◽  
Author(s):  
Tom R. Booker
Keyword(s):  
Evolutionary Genetics ◽  
Molecular Data ◽  
Substantial Contribution ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Relative Contribution ◽  
Standing Variation ◽  
Accuracy And Precision ◽  
New Mutations

Characterizing the distribution of fitness effects (DFE) for new mutations is central in evolutionary genetics. Analysis of molecular data under the McDonald-Kreitman test has suggested that adaptive substitutions make a substantial contribution to between-species divergence. Methods have been proposed to estimate the parameters of the distribution of fitness effects for positively selected mutations from the unfolded site frequency spectrum (uSFS). Such methods perform well when beneficial mutations are mildly selected and frequent. However, when beneficial mutations are strongly selected and rare, they may make little contribution to standing variation and will thus be difficult to detect from the uSFS. In this study, I analyze uSFS data from simulated populations subject to advantageous mutations with effects on fitness ranging from mildly to strongly beneficial. As expected, frequent, mildly beneficial mutations contribute substantially to standing genetic variation and parameters are accurately recovered from the uSFS. However, when advantageous mutations are strongly selected and rare, there are very few segregating in populations at any one time. Fitting the uSFS in such cases leads to underestimates of the strength of positive selection and may lead researchers to false conclusions regarding the relative contribution adaptive mutations make to molecular evolution. Fortunately, the parameters for the distribution of fitness effects for harmful mutations are estimated with high accuracy and precision. The results from this study suggest that the parameters of positively selected mutations obtained by analysis of the uSFS should be treated with caution and that variability at linked sites should be used in conjunction with standing variability to estimate parameters of the distribution of fitness effects in the future.

scholarly journals Haplotype-based inference of the distribution of fitness effects

Genetics ◽  
2022 ◽  
Author(s):  
Diego Ortega-Del Vecchyo ◽  
Kirk E Lohmueller ◽  
John Novembre
Keyword(s):  
Negative Selection ◽  
Low Frequency ◽  
Human Genetic Variation ◽  
Pairwise Identity ◽  
Fitness Effects ◽  
Sequencing Studies ◽  
Identity By State ◽  
Source Of Information ◽  
New Framework ◽  
New Mutations

Abstract Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some non-equilibrium populations (such as those that have had recent population expansions) it is possible to distinguish between positive or negative selection acting on a set of variants. With our new framework, one can infer a fixed selection intensity acting on a set of variants at a particular frequency, or a distribution of selection coefficients for standing variants and new mutations. We show an application of our method to the UK10K phased haplotype dataset of individuals.

scholarly journals Gene expression drives the evolution of dominance

2017 ◽  
Author(s):  
Christian D. Huber ◽  
Arun Durvasula ◽  
Angela M. Hancock ◽  
Kirk E. Lohmueller
Keyword(s):  
Complex Traits ◽  
Mating Systems ◽  
Multiple Mating ◽  
Expression Patterns ◽  
Natural Populations ◽  
Deleterious Mutations ◽  
Fitness Effects ◽  
Population Genomic ◽  
Degree Of Dominance ◽  
New Mutations

AbstractDominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance has yet to be quantified in natural populations. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arose as the inevitable consequence of the functional importance of genes and their optimal expression levels.One sentence summaryWe use population genomic data to characterize the degree of dominance for new mutations and develop a new theory for its evolution.

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