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 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 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.

scholarly journals Deleterious variation mimics signatures of genomic incompatibility and adaptive introgression

2017 ◽  
Author(s):  
Bernard Y. Kim ◽  
Christian D. Huber ◽  
Kirk E. Lohmueller
Keyword(s):  
Population Genetic ◽  
Natural Populations ◽  
Genetic Load ◽  
Population Admixture ◽  
Population Differences ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Adaptive Introgression ◽  
Fitness Effects ◽  
New Mutations

AbstractWhile it is appreciated that population size changes can impact patterns of deleterious variation in natural populations, less attention has been paid to how population admixture affects the dynamics of deleterious variation. Here we use population genetic simulations to examine how admixture impacts deleterious variation under a variety of demographic scenarios, dominance coefficients, and recombination rates. Our results show that gene flow between populations can temporarily reduce the genetic load of smaller populations, especially if deleterious mutations are recessive. Additionally, when fitness effects of new mutations are recessive, between-population differences in the sites at which deleterious variants exist creates heterosis in hybrid individuals. This can lead to an increase in introgressed ancestry, particularly when recombination rates are low. Under certain scenarios, introgressed ancestry can increase from an initial frequency of 5% to 30-75% and fix at many loci, even in the absence of beneficial mutations. Further, deleterious variation and admixture can generate correlations between the frequency of introgressed ancestry and recombination rate or exon density, even in the absence of other types of selection. The direction of these correlations is determined by the specific demography and whether mutations are additive or recessive. Therefore, it is essential that null models include both demography and deleterious variation before invoking reproductive incompatibilities or adaptive introgression to explain unusual patterns of genetic variation.

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

Genetics ◽  
2021 ◽  
Author(s):  
Kimberly J Gilbert ◽  
Stefan Zdraljevic ◽  
Daniel E Cook ◽  
Asher D Cutter ◽  
Erik C Andersen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Caenorhabditis Elegans ◽  
Population Size ◽  
Random Mating ◽  
Genome Structure ◽  
Population Substructure ◽  
C Elegans ◽  
Fitness Effects ◽  
Self Fertilization ◽  
New Mutations

Abstract The 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, genome structure, 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 on linked sites can conspire to compromise estimates of the DFE from extant polymorphisms with existing methods. 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.

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