scholarly journals Causes of natural variation in fitness: Evidence from studies of Drosophila populations

2015 ◽  
Vol 112 (6) ◽  
pp. 1662-1669 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Population Genetics ◽  
Genetic Variation ◽  
Balancing Selection ◽  
Large Contribution ◽  
Deleterious Mutations ◽  
Weak Selection ◽  
Fitness Components ◽  
Genetic Studies ◽  
Standing Variation ◽  
Available Information

DNA sequencing has revealed high levels of variability within most species. Statistical methods based on population genetics theory have been applied to the resulting data and suggest that most mutations affecting functionally important sequences are deleterious but subject to very weak selection. Quantitative genetic studies have provided information on the extent of genetic variation within populations in traits related to fitness and the rate at which variability in these traits arises by mutation. This paper attempts to combine the available information from applications of the two approaches to populations of the fruitfly Drosophila in order to estimate some important parameters of genetic variation, using a simple population genetics model of mutational effects on fitness components. Analyses based on this model suggest the existence of a class of mutations with much larger fitness effects than those inferred from sequence variability and that contribute most of the standing variation in fitness within a population caused by the input of mildly deleterious mutations. However, deleterious mutations explain only part of this standing variation, and other processes such as balancing selection appear to make a large contribution to genetic variation in fitness components in Drosophila.

scholarly journals An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components

2017 ◽  
Author(s):  
Nathaniel P. Sharp ◽  
Aneil F. Agrawal
Keyword(s):  
Genetic Variance ◽  
Balancing Selection ◽  
Statistical Tests ◽  
Balance Model ◽  
Male Mating ◽  
Deleterious Mutations ◽  
Fitness Component ◽  
Fitness Components ◽  
Female Fecundity ◽  
Mutational Variance

ABSTRACTDespite decades of research, the factors that maintain genetic variation for fitness are poorly understood. Mutation selection balance will always contribute to standing variance, but it is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to mutation-selection balance can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the actual standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the mutation-selection balance model, and could be used to identify traits or populations where genetic variance is maintained by factors beyond mutation-selection balance. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. To encourage the application of this approach, we describe the underlying theory and use it to test the mutation selection balance model for three traits in Drosophila melanogaster. We find some evidence for non-mutational variance in male mating success and female fecundity relative to larval viability, which is consistent with balancing selection on sexual fitness components. Finally, we discuss the theoretical and practical limitations to this approach, and discuss how to apply it successfully.

scholarly journals A non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster exhibits antagonistically pleiotropic fitness effects

2021 ◽  
Vol 288 (1950) ◽  
Author(s):  
Michael D. Jardine ◽  
Filip Ruzicka ◽  
Charlotte Diffley ◽  
Kevin Fowler ◽  
Max Reuter
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Variation ◽  
Balancing Selection ◽  
Antagonistic Pleiotropy ◽  
Multiple Target ◽  
Indel Polymorphism ◽  
Fitness Components ◽  
Fitness Effects ◽  
Males And Females ◽  
Opposing Effects

The amount of genetic variation for fitness within populations tends to exceed that expected under mutation–selection–drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here, we identify a non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster and measure survival and reproductive components of fitness in males and females of replicate lines carrying each respective allele. Expressing the fruitless region in a hemizygous state reveals a pattern of AP, with one allele generating greater reproductive fitness and the other conferring greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, which may reflect dominance reversal and/or epistasis. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as fruitless , may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.

scholarly journals An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components

2018 ◽  
Vol 285 (1890) ◽  
pp. 20181864 ◽  
Author(s):  
Nathaniel P. Sharp ◽  
Aneil F. Agrawal
Keyword(s):  
Genetic Variance ◽  
Balancing Selection ◽  
Statistical Tests ◽  
Balance Model ◽  
Male Mating ◽  
Male Mating Success ◽  
Deleterious Mutations ◽  
Fitness Component ◽  
Fitness Components ◽  
Female Fecundity

Despite decades of research, the factors that maintain genetic variation for fitness are poorly understood. It is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance (MSB) and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to MSB can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the MSB model, and could be used to identify traits or populations where genetic variance is maintained by other factors. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. We describe the underlying theory and use it to test the MSB model for three traits in Drosophila melanogaster . We find evidence for differences among traits, with MSB being sufficient to explain genetic variance in larval viability but not male mating success or female fecundity. Our results are consistent with balancing selection on sexual fitness components, and demonstrate the feasibility of rigorous statistical tests of the MSB model.

scholarly journals A non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster exhibits antagonistically pleiotropic fitness effects

2020 ◽  
Author(s):  
Michael D. Jardine ◽  
Filip Ruzicka ◽  
Charlotte Diffley ◽  
Kevin Fowler ◽  
Max Reuter
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Variation ◽  
Balancing Selection ◽  
The Other ◽  
Antagonistic Pleiotropy ◽  
Indel Polymorphism ◽  
Fitness Components ◽  
Fitness Effects ◽  
Males And Females ◽  
Opposing Effects

AbstractThe amount of genetic variation for fitness within populations tends to exceed that expected under mutation-selection-drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here we identify a non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster and measure survival and reproductive components of fitness in males and females of replicate lines carrying one or the other allele. Expressing the fruitless region in a hemizygous state we observe a pattern of AP, with one allele resulting in greater reproductive fitness while the other confers greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, suggesting widespread epistatic effects. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as fruitless, may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.

scholarly journals The genetic basis of inbreeding depression

1999 ◽  
Vol 74 (3) ◽  
pp. 329-340 ◽  
Author(s):  
BRIAN CHARLESWORTH ◽  
DEBORAH CHARLESWORTH
Keyword(s):  
Inbreeding Depression ◽  
Genetic Basis ◽  
Significant Contribution ◽  
Balancing Selection ◽  
Genetic Data ◽  
Deleterious Mutations ◽  
Fitness Components ◽  
Mutation Pressure ◽  
Quantitative Genetic ◽  
Experimental Approaches

Data on the effects of inbreeding on fitness components are reviewed in the light of population genetic models of the possible genetic causes of inbreeding depression. Deleterious mutations probably play a major role in causing inbreeding depression. Putting together the different kinds of quantitative genetic data, it is difficult to account for the very large effects of inbreeding on fitness in Drosophila and outcrossing plants without a significant contribution from variability maintained by selection. Overdominant effects of alleles on fitness components seem not to be important in most cases. Recessive or partially recessive deleterious effects of alleles, some maintained by mutation pressure and some by balancing selection, thus seem to be the most important source of inbreeding depression. Possible experimental approaches to resolving outstanding questions are discussed.

The Effect of Selection on Genealogies

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 1115-1131 ◽  
Author(s):  
N H Barton ◽  
A M Etheridge
Keyword(s):  
Allele Frequency ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
Weak Selection ◽  
Random Drift ◽  
Genotype Frequencies ◽  
Coalescence Times

Abstract The coalescent process can describe the effects of selection at linked loci only if selection is so strong that genotype frequencies evolve deterministically. Here, we develop methods proposed by Kaplan, Darden, and Hudson to find the effects of weak selection. We show that the overall effect is given by an extension to Price’s equation: the change in properties such as moments of coalescence times is equal to the covariance between those properties and the fitness of the sample of genes. The distribution of coalescence times differs substantially between allelic classes, even in the absence of selection. However, the average coalescence time between randomly chosen genes is insensitive to the current allele frequency and is affected significantly by purifying selection only if deleterious mutations are common and selection is strong (i.e., the product of population size and selection coefficient, Ns > 3). Balancing selection increases mean coalescence times, but the effect becomes large only when mutation rates between allelic classes are low and when selection is extremely strong. Our analysis supports previous simulations that show that selection has surprisingly little effect on genealogies. Moreover, small fluctuations in allele frequency due to random drift can greatly reduce any such effects. This will make it difficult to detect the action of selection from neutral variation alone.

scholarly journals Characterization of Deleterious Mutations in Outcrossing Populations

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 945-956 ◽  
Author(s):  
Hong-Wen Deng
Keyword(s):  
Genetic Variation ◽  
Genetic Variance ◽  
Estimation Bias ◽  
Deleterious Mutations ◽  
Environmental Variance ◽  
Higher Power ◽  
Sib Mating ◽  
The Mean ◽  
Simulation Results

Abstract Deng and Lynch recently proposed estimating the rate and effects of deleterious genomic mutations from changes in the mean and genetic variance of fitness upon selfing/outcrossing in outcrossing/highly selfing populations. The utility of our original estimation approach is limited in outcrossing populations, since selfing may not always be feasible. Here we extend the approach to any form of inbreeding in outcrossing populations. By simulations, the statistical properties of the estimation under a common form of inbreeding (sib mating) are investigated under a range of biologically plausible situations. The efficiencies of different degrees of inbreeding and two different experimental designs of estimation are also investigated. We found that estimation using the total genetic variation in the inbred generation is generally more efficient than employing the genetic variation among the mean of inbred families, and that higher degree of inbreeding employed in experiments yields higher power for estimation. The simulation results of the magnitude and direction of estimation bias under variable or epistatic mutation effects may provide a basis for accurate inferences of deleterious mutations. Simulations accounting for environmental variance of fitness suggest that, under full-sib mating, our extension can achieve reasonably well an estimation with sample sizes of only ∼2000-3000.

scholarly journals Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 827
Author(s):  
Lisa J. Martin ◽  
D Woodrow Benson
Keyword(s):  
Genetic Variation ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Genetic Architecture ◽  
Congenital Heart ◽  
Rare Variants ◽  
Heart Defects ◽  
Genetic Origin ◽  
Genetic Studies ◽  
The Ideal

Congenital heart defects (CHD) are malformations present at birth that occur during heart development. Increasing evidence supports a genetic origin of CHD, but in the process important challenges have been identified. This review begins with information about CHD and the importance of detailed phenotyping of study subjects. To facilitate appropriate genetic study design, we review DNA structure, genetic variation in the human genome and tools to identify the genetic variation of interest. Analytic approaches powered for both common and rare variants are assessed. While the ideal outcome of genetic studies is to identify variants that have a causal role, a more realistic goal for genetic analytics is to identify variants in specific genes that influence the occurrence of a phenotype and which provide keys to open biologic doors that inform how the genetic variants modulate heart development. It has never been truer that good genetic studies start with good planning. Continued progress in unraveling the genetic underpinnings of CHD will require multidisciplinary collaboration between geneticists, quantitative scientists, clinicians, and developmental biologists.

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