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.

scholarly journals Inbreeding Load, Average Dominance and the Mutation Rate for Mildly Deleterious Alleles in Mimulus guttatus

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1885-1898 ◽  
Author(s):  
John H Willis
Keyword(s):  
Inbreeding Depression ◽  
Deleterious Mutations ◽  
Mimulus Guttatus ◽  
Fitness Component ◽  
Fitness Effects ◽  
Fitness Traits ◽  
Deleterious Alleles ◽  
Degree Of Dominance ◽  
Almost All ◽  
Load Average

Abstract The goal of this study is to provide information on the genetics of inbreeding depression in a primarily outcrossing population of Mimulus guttatus. Previous studies of this population indicate that there is tremendous inbreeding depression for nearly every fitness component and that almost all of this inbreeding depression is due to mildly deleterious alleles rather than recessive lethals or steriles. In this article I assayed the homozygous and heterozygous fitnesses of 184 highly inbred lines extracted from a natural population. Natural selection during the five generations of selfing involved in line formation essentially eliminated major deleterious alleles but was ineffective in purging alleles with minor fitness effects and did not appreciably diminish overall levels of inbreeding depression. Estimates of the average degree of dominance of these mildly deleterious alleles, obtained from the regression of heterozygous fitness on the sum of parental homozygous fitness, indicate that the detrimental alleles are partially recessive for most fitness traits, with h~∼0.15 for cumulative measures of fitness. The inbreeding load, B, for total fitness is ~1.0 in this experiment. These results are consistent with the hypothesis that spontaneous mildly deleterious mutations occur at a rate >0.1 mutation per genome per generation.

scholarly journals The genetic structure of natural populations of Drosophila melanogaster. XXIV. Effects of hybrid dysgenesis on the components of genetic variance of variability.

Genetics ◽  
1991 ◽  
Vol 127 (3) ◽  
pp. 545-552
Author(s):  
D S Suh ◽  
T Mukai
Keyword(s):  
Drosophila Melanogaster ◽  
Population Genetic ◽  
Genetic Parameters ◽  
Genetic Variance ◽  
Additive Genetic Variance ◽  
Natural Populations ◽  
Deleterious Mutations ◽  
Degree Of Dominance ◽  
Population Genetic Parameters ◽  
P Type

Abstract Eight hundred second chromosomes were extracted from the Ishigakijima population, one of the southernmost populations of Drosophila melanogaster in Japan. Half of them were extracted in Native cytoplasm (P-type), and half in Foreign cytoplasm (M-type). Various population-genetic parameters, including the frequency of lethal-carrying second chromosomes (Q = 0.235 for the Native; 0.218 for the Foreign), the allelism rate of lethal second chromosome (Ic = 0.0217 for the Native; 0.0134 for the Foreign), the homozygous detrimental and lethal loads (D = 0.179 for the Native; 0.270 for the Foreign; L = 0.262 for the Native; 0.240 for the Foreign), the average degree of dominance of mildly deleterious mutations (ĥE = 0.244 for the Native; 0.208 for the Foreign), and the components of genetic variance for viability [additive (sigma A2) and dominance (sigma D2)](ŝigma A2 = 0.0187 for the Native; 0.0172 for the Foreign; ŝigma D2 = 0.0005 for the Native; 0.0009 for the Foreign) were estimated. The data indicate that D was significantly larger and hE was significantly smaller in the Foreign cytoplasm. However, the estimates of additive and dominance variances were not significantly different between the two cytoplasms. The additive genetic variance for viability in the Ishigakijima population was greater than expected on the basis of mutation-selection balance confirming previous studies on papers of D. melanogaster in warm climates.

scholarly journals Selection on Accessible Chromatin Regions in Capsella grandiflora

2021 ◽  
Author(s):  
Robert Horvath ◽  
Emily B Josephs ◽  
Edouard Pesquet ◽  
John R Stinchcombe ◽  
Stephen I Wright ◽  
...  
Keyword(s):  
Evolutionary Processes ◽  
Regulatory Regions ◽  
Noncoding Regions ◽  
Fitness Effects ◽  
Population Genomic ◽  
Intergenic Regions ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations ◽  
Accessible Chromatin ◽  
New Mutations

Abstract Accurate estimates of genome-wide rates and fitness effects of new mutations are essential for an improved understanding of molecular evolutionary processes. Although eukaryotic genomes generally contain a large noncoding fraction, functional noncoding regions and fitness effects of mutations in such regions are still incompletely characterized. A promising approach to characterize functional noncoding regions relies on identifying accessible chromatin regions (ACRs) tightly associated with regulatory DNA. Here, we applied this approach to identify and estimate selection on ACRs in Capsella grandiflora, a crucifer species ideal for population genomic quantification of selection due to its favorable population demography. We describe a population-wide ACR distribution based on ATAC-seq data for leaf samples of 16 individuals from a natural population. We use population genomic methods to estimate fitness effects and proportions of positively selected fixations (α) in ACRs and find that intergenic ACRs harbor a considerable fraction of weakly deleterious new mutations, as well as a significantly higher proportion of strongly deleterious mutations than comparable inaccessible intergenic regions. ACRs are enriched for expression quantitative trait loci (eQTL) and depleted of transposable element insertions, as expected if intergenic ACRs are under selection because they harbor regulatory regions. By integrating empirical identification of intergenic ACRs with analyses of eQTL and population genomic analyses of selection, we demonstrate that intergenic regulatory regions are an important source of nearly neutral mutations. These results improve our understanding of selection on noncoding regions and the role of nearly neutral mutations for evolutionary processes in outcrossing Brassicaceae species.

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 Inference of the distribution of selection coefficients for new nonsynonymous mutations using large samples

2016 ◽  
Author(s):  
Bernard Y. Kim ◽  
Christian D. Huber ◽  
Kirk E. Lohmueller
Keyword(s):  
Frequency Spectrum ◽  
Mixture Distribution ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
Sequencing Project ◽  
Fitness Effects ◽  
Large Samples ◽  
Exome Sequencing Project ◽  
Number Of Individuals ◽  
New Mutations

ABSTRACTThe distribution of fitness effects (DFE) has considerable importance in population genetics. To date, estimates of the DFE come from studies using a small number of individuals. Thus, estimates of the proportion of moderately to strongly deleterious new mutations may be unreliable because such variants are unlikely to be segregating in the data. Additionally, the true functional form of the DFE is unknown, and estimates of the DFE differ significantly between studies. Here we present a flexible and computationally tractable method, called Fit∂a∂i, to estimate the DFE using the site frequency spectrum from a large number of individuals. We apply our approach to the frequency spectrum of 1300 Europeans from the Exome Sequencing Project ESP6400 dataset, 1298 Danes from the LuCamp dataset, and 432 Europeans from the 1000 Genomes Project to estimate the DFE of deleterious nonsynonymous mutations. We infer significantly fewer (0.38-0.84x) strongly deleterious mutations with selection coefficient |s| > 0.01 and more (1.24-1.43x) weakly deleterious mutations with selection coefficient |s| < 0.001 compared to previous estimates. Furthermore, a DFE that is a mixture distribution of a point mass at neutrality plus a gamma distribution fits best to two of the three datasets. Our results suggest that nearly neutral forces play a larger role in human evolution than previously thought.

scholarly journals On the Rate and Linearity of Viability Declines in Drosophila Mutation-Accumulation Experiments: Genomic Mutation Rates and Synergistic Epistasis Revisited

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 797-806 ◽  
Author(s):  
James D Fry
Keyword(s):  
Mutation Rate ◽  
Average Rate ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
High Rate ◽  
Deleterious Mutations ◽  
Order Of Magnitude ◽  
Contamination Event ◽  
Genomic Mutation ◽  
The 1960S

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

scholarly journals Estimation of Parameters of Deleterious Mutations in Partial Selfing or Partial Outcrossing Populations and in Nonequilibrium Populations

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1893-1906 ◽  
Author(s):  
Jian Li ◽  
Hong-Wen Deng
Keyword(s):  
Computer Simulations ◽  
Natural Populations ◽  
Deleterious Mutations ◽  
Selfing Rate ◽  
Estimation Of Parameters ◽  
Animal Populations ◽  
Rapid Pace ◽  
Dynamics Of Populations ◽  
Mutation And Selection

Abstract The Deng-Lynch method was developed to estimate the rate and effects of deleterious genomic mutations (DGM) in natural populations under the assumption that populations are either completely outcrossing or completely selfing and that populations are at mutation-selection (M-S) balance. However, in many plant and animal populations, selfing or outcrossing is often incomplete in that a proportion of populations undergo inbreeding while the rest are outcrossing. In addition, the degrees of deviation of populations from M-S balance are often not known. Through computer simulations, we investigated the robustness and the applicability of the Deng-Lynch method under different degrees of partial selfing or partial outcrossing and for nonequilibrium populations approaching M-S balance at different stages. The investigation was implemented under constant, variable, and epistatic mutation effects. We found that, generally, the estimation by the Deng-Lynch method is fairly robust if the selfing rate (S) is &lt;0.10 in outcrossing populations and if S &gt; 0.8 in selfing populations. The estimation may be unbiased under partial selfing with variable and epistatic mutation effects in predominantly outcrossing populations. The estimation is fairly robust in nonequilibrium populations at different stages approaching M-S balance. The dynamics of populations approaching M-S balance under various parameters are also studied. Under mutation and selection, populations approach balance at a rapid pace. Generally, it takes 400–2000 generations to reach M-S balance even when starting from homogeneous individuals free of DGM. Our investigation here provides a basis for characterizing DGM in partial selfing or outcrossing populations and for nonequilibrium populations.

scholarly journals The Rate of Mutation and the Homozygous and Heterozygous Mutational Effects for Competitive Viability: A Long-Term Experiment With Drosophila melanogaster

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 681-693 ◽  
Author(s):  
David Chavarrías ◽  
Carlos López-Fanjul ◽  
Aurora García-Dorado
Keyword(s):  
Drosophila Melanogaster ◽  
Minimum Distance ◽  
Deleterious Mutations ◽  
Regression Estimate ◽  
Term Experiment ◽  
Degree Of Dominance ◽  
Long Term Experiment ◽  
Rate Of Decline ◽  
Good Agreement

Abstract The effect of 250 generations of mutation accumulation (MA) on the second chromosome competitive viability of Drosophila melanogaster was analyzed both in homozygous and heterozygous conditions. We used full-sib MA lines, where selection hampers the accumulation of severely deleterious mutations but is ineffective against mildly deleterious ones. A large control population was simultaneously evaluated. Competitive viability scores, unaffected by the expression of mutations in heterozygosis, were obtained relative to a Cy/L2 genotype. The rate of decline in mean ΔM ≈ 0.1% was small. However, that of increase in variance ΔV ≈ 0.08 × 10-3 was similar to the values obtained in previous experiments when severely deleterious mutations were excluded. The corresponding estimates of the mutation rate λ ≥ 0.01 and the average effect of mutations E(s) ≤ 0.08 are in good agreement with Bateman-Mukai and minimum distance estimates for noncompetitive viability obtained from the same MA lines after 105 generations. Thus, competitive and noncompetitive viability show similar mutational properties. The regression estimate of the degree of dominance for mild-to-moderate deleterious mutations was ∼0.3, suggesting that the pertinent value for new unselected mutations should be somewhat smaller.

scholarly journals Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 899-909
Author(s):  
Rongling Wu ◽  
Zhao-Bang Zeng
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Traits ◽  
Positional Cloning ◽  
Genome Structure ◽  
Natural Populations ◽  
Linkage Disequilibrium Mapping ◽  
Linkage Disequilibria ◽  
Time Simulation ◽  
New Strategy ◽  
Fisher Scoring Algorithm

Abstract A new strategy for studying the genome structure and organization of natural populations is proposed on the basis of a combined analysis of linkage and linkage disequilibrium using known polymorphic markers. This strategy exploits a random sample drawn from a panmictic natural population and the open-pollinated progeny of the sample. It is established on the principle of gene transmission from the parental to progeny generation during which the linkage between different markers is broken down due to meiotic recombination. The strategy has power to simultaneously capture the information about the linkage of the markers (as measured by recombination fraction) and the degree of their linkage disequilibrium created at a historic time. Simulation studies indicate that the statistical method implemented by the Fisher-scoring algorithm can provide accurate and precise estimates for the allele frequencies, recombination fractions, and linkage disequilibria between different markers. The strategy has great implications for constructing a dense linkage disequilibrium map that can facilitate the identification and positional cloning of the genes underlying both simple and complex traits.

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