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.

scholarly journals The mutation load under tetrasomic inheritance and its consequences for the evolution of the selfing rate in autotetraploid species

1999 ◽  
Vol 74 (1) ◽  
pp. 31-42 ◽  
Author(s):  
J. RONFORT
Keyword(s):  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Stable State ◽  
Approximate Solutions ◽  
Balance Model ◽  
Deleterious Mutations ◽  
Selfing Rate ◽  
Mutation Load ◽  
Mean Fitness ◽  
The Mean

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

scholarly journals Genotype-environment interactions and the maintenance of polygenic variation.

Genetics ◽  
1989 ◽  
Vol 121 (1) ◽  
pp. 129-138 ◽  
Author(s):  
J H Gillespie ◽  
M Turelli
Keyword(s):  
Genetic Variance ◽  
Balancing Selection ◽  
Additive Genetic Variance ◽  
Natural Populations ◽  
Extensive Literature ◽  
Multilocus Genotype ◽  
Polygenic Inheritance ◽  
Mean Fitness ◽  
The Mean ◽  
Polygenic Variation

Abstract Genotype-environment interactions may be a potent force maintaining genetic variation in quantitative traits in natural populations. This is shown by a simple model of additive polygenic inheritance in which the additive contributions of alleles vary with the environment. Under simplifying symmetry assumptions, the model implies that the variance of the phenotypes produced across environments by a multilocus genotype decreases as the number of heterozygous loci increases. In the region of an optimal phenotype, the mapping from the quantitative trait into fitness is concave, and the mean fitness of a genotype will increase with the number of heterozygous loci. This leads to balancing selection, polymorphism, and potentially high levels of additive genetic variance, even though all allelic effects remain additive within each specific environment. An important implication of the model is that the variation maintained by genotype-environment interactions is difficult to study with the restricted range of environments represented in typical experiments. In particular, if fluctuations in allelic effects are pervasive, as suggested by the extensive literature on genotype-environment interactions, efforts to estimate genetic parameters in a single environment may be of limited value.

Estimation of Deleterious Genomic Mutation Parameters in Natural Populations by Accounting for Variable Mutation Effects Across Loci

Genetics ◽  
2002 ◽  
Vol 162 (3) ◽  
pp. 1487-1500 ◽  
Author(s):  
Hong-Wen Deng ◽  
Guimin Gao ◽  
Jin-Long Li
Keyword(s):  
Statistical Method ◽  
Mutation Rate ◽  
Genetic Variance ◽  
Natural Populations ◽  
Evolutionary Genetics ◽  
Simulation Studies ◽  
Fitness Effects ◽  
Mean Fitness ◽  
The Mean ◽  
Genomic Mutation

Abstract The genomes of all organisms are subject to continuous bombardment of deleterious genomic mutations (DGM). Our ability to accurately estimate various parameters of DGM has profound significance in population and evolutionary genetics. The Deng-Lynch method can estimate the parameters of DGM in natural selfing and outcrossing populations. This method assumes constant fitness effects of DGM and hence is biased under variable fitness effects of DGM. Here, we develop a statistical method to estimate DGM parameters by considering variable mutation effects across loci. Under variable mutation effects, the mean fitness and genetic variance for fitness of parental and progeny generations across selfing/outcrossing in outcrossing/selfing populations and the covariance between mean fitness of parents and that of their progeny are functions of DGM parameters: the genomic mutation rate U, average homozygous effect s, average dominance coefficient h, and covariance of selection and dominance coefficients cov(h, s). The DGM parameters can be estimated by the algorithms we developed herein, which may yield improved estimation of DGM parameters over the Deng-Lynch method as demonstrated by our simulation studies. Importantly, this method is the first one to characterize cov(h, s) for DGM.

The Contemporary Evolution of Fitness

2018 ◽  
Vol 49 (1) ◽  
pp. 457-476 ◽  
Author(s):  
Andrew P. Hendry ◽  
Daniel J. Schoen ◽  
Matthew E. Wolak ◽  
Jane M. Reid
Keyword(s):  
Genetic Variance ◽  
Evolutionary Dynamics ◽  
Additive Genetic Variance ◽  
Deleterious Mutations ◽  
Contemporary Evolution ◽  
Evolutionary Potential ◽  
Empirical Estimates ◽  
Evolutionary Rescue ◽  
Proportional Change ◽  
Mean Fitness

The rate of evolution of population mean fitness informs how selection acting in contemporary populations can counteract environmental change and genetic degradation (mutation, gene flow, drift, recombination). This rate influences population increases (e.g., range expansion), population stability (e.g., cryptic eco-evolutionary dynamics), and population recovery (i.e., evolutionary rescue). We review approaches for estimating such rates, especially in wild populations. We then review empirical estimates derived from two approaches: mutation accumulation (MA) and additive genetic variance in fitness (IAw). MA studies inform how selection counters genetic degradation arising from deleterious mutations, typically generating estimates of <1% per generation. IAw studies provide an integrated prediction of proportional change per generation, nearly always generating estimates of <20% and, more typically, <10%. Overall, considerable, but not unlimited, evolutionary potential exists in populations facing detrimental environmental or genetic change. However, further studies with diverse methods and species are required for more robust and general insights.

scholarly journals Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli

2010 ◽  
Vol 365 (1544) ◽  
pp. 1177-1186 ◽  
Author(s):  
Sandra Trindade ◽  
Lilia Perfeito ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Estimation Methods ◽  
Single Individual ◽  
Deleterious Mutations ◽  
Spontaneous Mutations ◽  
Mutator Strain ◽  
Mean Fitness

Knowledge of the mutational parameters that affect the evolution of organisms is of key importance in understanding the evolution of several characteristics of many natural populations, including recombination and mutation rates. In this study, we estimated the rate and mean effect of spontaneous mutations that affect fitness in a mutator strain of Escherichia coli and review some of the estimation methods associated with mutation accumulation (MA) experiments. We performed an MA experiment where we followed the evolution of 50 independent mutator lines that were subjected to repeated bottlenecks of a single individual for approximately 1150 generations. From the decline in mean fitness and the increase in variance between lines, we estimated a minimum mutation rate to deleterious mutations of 0.005 (±0.001 with 95% confidence) and a maximum mean fitness effect per deleterious mutation of 0.03 (±0.01 with 95% confidence). We also show that any beneficial mutations that occur during the MA experiment have a small effect on the estimate of the rate and effect of deleterious mutations, unless their rate is extremely large. Extrapolating our results to the wild-type mutation rate, we find that our estimate of the mutational effects is slightly larger and the inferred deleterious mutation rate slightly lower than previous estimates obtained for non-mutator E. coli .

scholarly journals GENETIC LOAD IN NATURAL POPULATIONS: IS IT COMPATIBLE WITH THE HYPOTHESIS THAT MANY POLYMORPHISMS ARE MAINTAINED BY NATURAL SELECTION?

Genetics ◽  
1974 ◽  
Vol 77 (3) ◽  
pp. 569-589
Author(s):  
Martin L Tracey ◽  
Francisco J Ayala
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Selection ◽  
Natural Population ◽  
Natural Populations ◽  
Genetic Load ◽  
Structural Genes ◽  
Invertebrate Species ◽  
Average Proportion ◽  
Mean Fitness ◽  
The Mean

ABSTRACT Recent studies of genetically controlled enzyme variation lead to an estimation that at least 30 to 60% of the structural genes are polymorphic in natural populations of many vertebrate and invertebrate species. Some authors have argued that a substantial proportion of these polymorphisms cannot be maintained by natural selection because this would result in an unbearable genetic load. If many polymorphisms are maintained by heterotic natural selection, individuals with much greater than average proportion of homozygous loci should have very low fitness. We have measured in Drosophila melanogaster the fitness of flies homozygous for a complete chromosome relative to normal wild flies. A total of 37 chromosomes from a natural population have been tested using 92 experimental populations. The mean fitness of homozygous flies is 0.12 for second chromosomes, and 0.13 for third chromosomes. These estimates are compatible with the hypothesis that many (more than one thousand) loci are maintained by heterotic selection in natural populations of D. melanogaster.

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 Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter

2000 ◽  
Vol 75 (1) ◽  
pp. 75-81 ◽  
Author(s):  
THOMAS BATAILLON ◽  
MARK KIRKPATRICK
Keyword(s):  
Population Size ◽  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Large Population ◽  
Genetic Load ◽  
Breeding Systems ◽  
Deleterious Mutations ◽  
Single Locus Analysis ◽  
Population Sizes ◽  
Inbreeding Rate

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

scholarly journals Properties of spontaneous mutations affecting quantitative traits

1999 ◽  
Vol 74 (3) ◽  
pp. 341-350 ◽  
Author(s):  
A. GARCÍA-DORADO ◽  
C. LÓPEZ-FANJUL ◽  
A. CABALLERO
Keyword(s):  
Deleterious Mutation ◽  
Natural Populations ◽  
Detectable Effect ◽  
Environment Interaction ◽  
Fitness Component ◽  
Standing Variation ◽  
Genotype Environment Interaction ◽  
Component Traits ◽  
Mutational Variance ◽  
New Mutations

Recent mutation accumulation results from invertebrate species suggest that mild deleterious mutation is far less frequent than previously thought, implying smaller expressed mutational loads. Although the rate (λ) and effect (s) of very slight deleterious mutation remain unknown, most mutational fitness decline would come from moderately deleterious mutation (s ≈ 0·2, λ ≈ 0·03), and this situation would not qualitatively change in harsh environments. Estimates of the average coefficient of dominance (h¯) of non-severe deleterious mutations are controversial. The typical value of h¯ = 0·4 can be questioned, and a lower estimate (about 0·1) is suggested. Estimated mutational parameters are remarkably alike for morphological and fitness component traits (excluding lethals), indicating low mutation rates and moderate mutational effects, with a distribution generally showing strong negative asymmetry and little leptokurtosis. New mutations showed considerable genotype–environment interaction. However, the mutational variance of fitness-component traits due to non-severe detrimental mutations did not increase with environmental harshness. For morphological traits, a class of predominantly additive mutations with no detectable effect on fitness and relatively small effect on the trait was identified. This should be close to that responsible for standing variation in natural populations.

scholarly journals An Upper Limit on the Functional Fraction of the Human Genome

2017 ◽  
Vol 9 (7) ◽  
pp. 1880-1885 ◽  
Author(s):  
Dan Graur
Keyword(s):  
Human Genome ◽  
Human Population ◽  
Mutational Load ◽  
Deleterious Mutations ◽  
Replacement Level ◽  
Functional Regions ◽  
Upper Limit ◽  
Constant Size ◽  
Mean Fitness ◽  
The Mean

AbstractFor the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 15%.

Sign in / Sign up

Export Citation Format

Share Document