scholarly journals The Effects on Neutral Variability of Recurrent Selective Sweeps and Background Selection

Genetics ◽  
2019 ◽  
Vol 212 (1) ◽  
pp. 287-303 ◽  
Author(s):  
José Luis Campos ◽  
Brian Charlesworth
Keyword(s):  
Background Selection ◽  
Selective Sweeps

Chromosomal Patterns of Microsatellite Variability Contrast Sharply in African and Non-African Populations of Drosophila melanogaster

Genetics ◽  
2002 ◽  
Vol 160 (1) ◽  
pp. 247-256
Author(s):  
M Kauer ◽  
B Zangerl ◽  
D Dieringer ◽  
C Schlötterer
Keyword(s):  
Chromosomal Polymorphism ◽  
Background Selection ◽  
Selective Sweeps ◽  
X Chromosomes ◽  
Evolutionary Forces ◽  
Relative Contribution ◽  
African Populations ◽  
Neutral Variation ◽  
Colonization Process ◽  
The Subject

Abstract Levels of neutral variation are influenced by background selection and hitchhiking. The relative contribution of these evolutionary forces to the distribution of neutral variation is still the subject of ongoing debates. Using 133 microsatellites, we determined levels of variability on X chromosomes and autosomes in African and non-African D. melanogaster populations. In the ancestral African populations microsatellite variability was higher on X chromosomes than on autosomes. In non-African populations X-linked polymorphism is significantly more reduced than autosomal variation. In non-African populations we observed a significant positive correlation between X chromosomal polymorphism and recombination rate. These results are consistent with the interpretation that background selection shapes levels of neutral variability in the ancestral populations, while the pattern in derived populations is determined by multiple selective sweeps during the colonization process. Further research, however, is required to investigate the influence of inversion polymorphisms and unequal sex ratios.

Selection on X-linked Genes During Speciation in the Drosophila athabasca Complex

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 689-703 ◽  
Author(s):  
Michael J Ford ◽  
Charles F Aquadro
Keyword(s):  
Computer Simulation ◽  
Natural Selection ◽  
Molecular Evolution ◽  
Restriction Site ◽  
Neutral Model ◽  
Background Selection ◽  
Selective Sweeps ◽  
Differential Migration ◽  
Site Survey ◽  
Low Levels

Abstract We present the results of a restriction site survey of variation at five loci in Drosophila athabasca, complimenting a previous study of the period locus. There is considerably greater differentiation between the three semispecies of D. athabasca at the period locus and two other X-linked genes (neon-transient-A and E74A) than at three autosomal genes (Xdh, Adh and RC98). Using a modification of the HKA test, which uses fixed differences between the semispecies and a test based on differences in Fst among loci, we show that the greater differentiation of the X-linked loci compared with the autosomal loci is inconsistent with a neutral model of molecular evolution. We explore several evolutionary scenarios by computer simulation, including differential migration of X and autosomal genes, very low levels of migration among the semispecies, selective sweeps, and background selection, and conclude that X-linked selective sweeps in at least two of the semispecies are the best explanation for the data. This evidence that natural selection acted on the X-chromosome suggests that another X-linked trait, mating song differences among the semispecies, may have been the target of selection.

scholarly journals Detecting recent selective sweeps while controlling for mutation rate and background selection

2015 ◽  
Vol 25 (1) ◽  
pp. 142-156 ◽  
Author(s):  
Christian D. Huber ◽  
Michael DeGiorgio ◽  
Ines Hellmann ◽  
Rasmus Nielsen
Keyword(s):  
Mutation Rate ◽  
Background Selection ◽  
Selective Sweeps

scholarly journals The Effect of Mating System Differences on Nucleotide Diversity at the Phosphoglucose Isomerase Locus in the Plant Genus Leavenworthia

Genetics ◽  
1999 ◽  
Vol 151 (1) ◽  
pp. 343-357 ◽  
Author(s):  
F Liu ◽  
D Charlesworth ◽  
M Kreitman
Keyword(s):  
Genetic Diversity ◽  
Nucleotide Diversity ◽  
Phosphoglucose Isomerase ◽  
Self Incompatibility ◽  
Background Selection ◽  
Selective Sweeps ◽  
Balanced Polymorphism ◽  
Neutral Genetic Diversity ◽  
Low Diversity ◽  
High Diversity

AbstractTo test the theoretical prediction that highly inbreeding populations should have low neutral genetic diversity relative to closely related outcrossing populations, we sequenced portions of the cytosolic phosphoglucose isomerase (PgiC) gene in the plant genus Leavenworthia, which includes both self-incompatible and inbreeding taxa. On the basis of sequences of intron 12 of this gene, the expected low diversity was seen in both populations of the selfers Leavenworthia uniflora and L. torulosa and in three highly inbreeding populations of L. crassa, while high diversity was found in self-incompatible L. stylosa, and moderate diversity in L. crassa populations with partial or complete self-incompatibility. In L. stylosa, the nucleotide diversity was strongly structured into three haplotypic classes, differing by several insertion/deletion sequences, with linkage disequilibrium between sequences of the three types in intron 12, but not in the adjacent regions. Differences between the three kinds of haplotypes are larger than between sequences of this gene region from different species. The haplotype divergence suggests the presence of a balanced polymorphism at this locus, possibly predating the split between L. stylosa and its two inbreeding sister taxa, L. uniflora and L. torulosa. It is therefore difficult to distinguish between different potential causes of the much lower sequence diversity at this locus in inbreeding than outcrossing populations. Selective sweeps during the evolution of these populations are possible, or background selection, or merely loss of a balanced polymorphism maintained by overdominance in the populations that evolved high selfing rates.

scholarly journals Understanding the factors that shape patterns of nucleotide diversity in the house mouse genome

2018 ◽  
Author(s):  
Tom R. Booker ◽  
Peter D. Keightley
Keyword(s):  
House Mouse ◽  
Nucleotide Diversity ◽  
Mouse Genome ◽  
Parameter Estimates ◽  
Background Selection ◽  
Selective Sweeps ◽  
Functional Elements ◽  
Protein Coding ◽  
Wild Mice ◽  
Protein Coding Genes

AbstractA major goal of population genetics has been to determine the extent to which selection at linked sites influences patterns of neutral nucleotide diversity in the genome. Multiple lines of evidence suggest that diversity is influenced by both positive and negative selection. For example, in many species there are troughs in diversity surrounding functional genomic elements, consistent with the action of either background selection (BGS) or selective sweeps. In this study, we investigated the causes of the diversity troughs that are observed in the wild house mouse genome. Using the unfolded site frequency spectrum (uSFS), we estimated the strength and frequencies of deleterious and advantageous mutations occurring in different functional elements in the genome. We then used these estimates to parameterize forward-in-time simulations of chromosomes, using realistic distributions of functional elements and recombination rate variation in order to determine if selection at linked sites can explain the observed patterns of nucleotide diversity. The simulations suggest that BGS alone cannot explain the dips in diversity around either exons or conserved non-coding elements (CNEs). A combination of BGS and selective sweeps, however, can explain the troughs in diversity around CNEs. This is not the case for protein-coding exons, where observed dips in diversity cannot be explained by parameter estimates obtained from the uSFS. We discuss the extent to which our results provide evidence of sweeps playing a role in shaping patterns of nucleotide diversity and the limitations of using the uSFS for obtaining inferences of the frequency and effects of advantageous mutations.Author SummaryWe present a study examining the causes of variation in nucleotide diversity across the mouse genome. The status of mice as a model organism in the life sciences makes them an excellent model system for studying molecular evolution in mammals. In our study, we analyse how natural selection acting on new mutations can affect levels of nucleotide diversity through the processes of background selection and selective sweeps. To perform our analyses, we first estimated the rate and strengths of selected mutations from a sample of wild mice and then use our estimates in realistic population genetic simulations. Analysing simulations, we find that both harmful and beneficial mutations are required to explain patterns of nucleotide diversity in regions of the genome close to gene regulatory elements. For protein-coding genes, however, our approach is not able to fully explain observed patterns and we think that this is because there are strongly advantageous mutations that occur in protein-coding genes that we were not able to detect.

scholarly journals The effects on neutral variability of recurrent selective sweeps and background selection

2018 ◽  
Author(s):  
José Luis Campos ◽  
Brian Charlesworth
Keyword(s):  
Adaptive Evolution ◽  
Selective Sweep ◽  
Crossing Over ◽  
Background Selection ◽  
Selective Sweeps ◽  
Population Genomic ◽  
Approximate Integral ◽  
Theoretical Predictions ◽  
Site Diversity ◽  
Coalescent Time

ABSTRACTLevels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by selective sweeps or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, in order to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies – that the time occupied by a selective sweep is negligible compared with the neutral coalescent time. We derive a new expression for the expected level of neutral variability in the presence of recurrent selective sweeps and background selection. We also derive approximate integral expressions for the effects of recurrent selective sweeps. The accuracy of the theoretical predictions was tested against multilocus simulations, with selection, recombination and mutation parameters that are realistic for Drosophila melanogaster. In the presence of crossing over, there is approximate agreement between the theoretical and simulation results. We show that the observed relations between the rate of crossing over and the level of synonymous site diversity and rate of adaptive evolution in Drosophila are probably mainly caused by background selection, whereas selective sweeps and population size changes are needed to produce the observed distortions of the site frequency spectrum.

scholarly journals A New Model of Genetic Variation and Evolution Evaluates Relative Impacts of Background Selections and Selective Sweeps

2020 ◽  
Author(s):  
Xun Gu
Keyword(s):  
Genetic Diversity ◽  
Genetic Variation ◽  
Neutral Theory ◽  
Population Diversity ◽  
Simple Relationship ◽  
Small Contribution ◽  
Background Selection ◽  
Selective Sweeps ◽  
Recombination Rates ◽  
The One

AbstractIntra-population genetic variation and interspecies divergence in chromosome regions can be considerably affected by different local recombination rates. There are two models: (i) the selective sweeps that reduces the genetic diversity at linked sites and elevates the divergence rate; and (ii) the background selection that reduces the genetic diversity at linked sites and divergence rate. An intriguing question, yet highly controversial, is which one is dominant. In this paper, I develop a framework of generalize background selection, formulated by a diffusion model with two killing functions: the one associated with (negative) background selection is the rate to stop a fixation process of a mutation randomly, and the other associated with positive background selection (selective sweep) is the rate to stop a loss process of a mutation randomly. A simple relationship between the level of reduced diversity and the rate of divergence is derived, depending on the strength of generalized background selection (G) and the proportion of positive background selection (β). We analyzed the interspecies divergence and intra-population diversity in low-recombination regions of three organisms (fruitfly, soybean and human). Strikingly, all datasets demonstrated the dominance of (negative) background selection, and the positive background selection (selective sweeps) only has a small contribution (β∼10%). However, our analysis rejects the notion of β=0, namely, a complete negative background selection is unlikely. These findings may shed some lights on the long-term debates around Neutral Theory.

scholarly journals Detecting recent selective sweeps while controlling for mutation rate and background selection

2015 ◽  
Author(s):  
Christian D. Huber ◽  
Michael DeGiorgio ◽  
Ines Hellmann ◽  
Rasmus Nielsen
Keyword(s):  
Spatial Pattern ◽  
Mutation Rate ◽  
Composite Likelihood ◽  
Causative Mutation ◽  
Rate Variation ◽  
Ratio Test ◽  
Background Selection ◽  
Selective Sweeps ◽  
Effective Population ◽  
A Genome

A composite likelihood ratio test implemented in the program SweepFinder is a commonly used method for scanning a genome for recent selective sweeps. SweepFinder uses information on the spatial pattern of the site frequency spectrum (SFS) around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest to add fixed differences relative to an outgroup to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection modeled as a local reduction in the effective population size. Using simulations we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

scholarly journals Estimating the parameters of background selection and selective sweeps in Drosophila in the presence of gene conversion

2017 ◽  
Vol 114 (24) ◽  
pp. E4762-E4771 ◽  
Author(s):  
José Luis Campos ◽  
Lei Zhao ◽  
Brian Charlesworth
Keyword(s):  
Positive Selection ◽  
Gene Conversion ◽  
Major Effect ◽  
Selective Constraint ◽  
Background Selection ◽  
Selective Sweeps ◽  
Low Levels ◽  
Whole Genome Resequencing ◽  
Site Diversity ◽  
New Mutations

We used whole-genome resequencing data from a population of Drosophila melanogaster to investigate the causes of the negative correlation between the within-population synonymous nucleotide site diversity (πS) of a gene and its degree of divergence from related species at nonsynonymous nucleotide sites (KA). By using the estimated distributions of mutational effects on fitness at nonsynonymous and UTR sites, we predicted the effects of background selection at sites within a gene on πS and found that these could account for only part of the observed correlation between πS and KA. We developed a model of the effects of selective sweeps that included gene conversion as well as crossing over. We used this model to estimate the average strength of selection on positively selected mutations in coding sequences and in UTRs, as well as the proportions of new mutations that are selectively advantageous. Genes with high levels of selective constraint on nonsynonymous sites were found to have lower strengths of positive selection and lower proportions of advantageous mutations than genes with low levels of constraint. Overall, background selection and selective sweeps within a typical gene reduce its synonymous diversity to ∼75% of its value in the absence of selection, with larger reductions for genes with high KA. Gene conversion has a major effect on the estimates of the parameters of positive selection, such that the estimated strength of selection on favorable mutations is greatly reduced if it is ignored.

scholarly journals Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements

2021 ◽  
Author(s):  
David Murphy ◽  
Eyal Elyashiv ◽  
Guy Amster ◽  
Guy Sella
Keyword(s):  
Genetic Diversity ◽  
Purifying Selection ◽  
Dominant Mode ◽  
Background Selection ◽  
Selective Sweeps ◽  
Deleterious Mutations ◽  
Phylogenetic Conservation ◽  
Neutral Genetic Diversity ◽  
Polymorphism Data ◽  
Linked Selection

Analyses of genetic variation in many taxa have established that neutral genetic diversity is shaped by natural selection at linked sites. Whether the source of selection is primarily the fixation of strongly beneficial alleles (selective sweeps) or purifying selection on deleterious mutations (background selection) remains unknown, however. We address this question in humans by fitting a model of the joint effects of selective sweeps and background selection to autosomal polymorphism data from the 1000 Genomes Project. After controlling for variation in mutation rates along the genome, a model of background selection alone explains ~60% of the variance in diversity levels at the megabase scale. Adding the effects of selective sweeps driven by adaptive substitutions to the model does not improve the fit, and when both modes of selection are considered jointly, selective sweeps are estimated to have had little or no effect on linked neutral diversity. The regions under purifying selection are best predicted by phylogenetic conservation, with ~80% of the deleterious mutations affecting neutral diversity occurring in non-exonic regions. Thus, background selection is the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.

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